Surgical system and procedure for treatment of the trabecular meshwork and schlemm&#39;s canal using a femtosecond laser

ABSTRACT

A target volume of ocular tissue is treated with a laser having a direction of propagation toward the target volume, where the target volume is characterized by a distal extent, a proximal extent, and a lateral extent. A layer of tissue at an initial depth corresponding to the distal extent of the target volume is initially photodisrupted using a femtosecond laser by scanning the laser in multiple directions defining an initial treatment plane. Tissue at one or more subsequent depths between the distal extent of the target volume and the proximal extent of the target volume is subsequently photodisrupted using a femtosecond laser by moving a focus of the laser in a direction opposite the direction of propagation of the laser and then scanning the laser in multiple directions defining an subsequent treatment plane. Photodisruption is repeated at different subsequent depths until tissue at the proximal extent of the target volume is photodisrupted.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a divisional application of U.S. patent applicationSer. No. 16/674,850, filed Nov. 5, 2019, for “Surgical System andProcedure for Treatment of the Trabecular Meshwork and Schlemm's CanalUsing a Femtosecond Laser,” which is a continuation-in-part of each ofU.S. patent application Ser. No. 16/036,833, filed Jul. 16, 2018, for“Integrated Surgical System and Method for Treatment in theIrido-Corneal Angle of the Eye,” and U.S. patent application Ser. No.16/125,588, filed Sep. 7, 2018, for “Non-Invasive and Minimally InvasiveLaser Surgery for the Reduction of Intraocular Pressure in the Eye,” theentire disclosures of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates generally to the field of medical devicesand treatment of diseases in ophthalmology including glaucoma, and moreparticularly to systems, apparatuses, and methods for treating thetrabecular meshwork and Schlemm's canal using a femtosecond laser.

BACKGROUND

Before describing the different types of glaucoma and current diagnosisand treatments options, a brief overview of the anatomy of the eye isprovided.

Anatomy of the Eye

With reference to FIGS. 1-3, the outer tissue layer of the eye 1includes a sclera 2 that provides the structure of the eye's shape. Infront of the sclera 2 is a cornea 3 that is comprised of transparentlayers of tissue that allow light to enter the interior of the eye.Inside the eye 1 is a crystalline lens 4 that is connected to the eye byfiber zonules 5, which are connected to the ciliary body 6. Between thecrystalline lens 4 and the cornea 3 is an anterior chamber 7 thatcontains a flowing clear liquid called aqueous humor 8. Encircling theperimeter of the crystalline lens 4 is an iris 9 which forms a pupilaround the approximate center of the crystalline lens. A posteriorchamber 23 is an annular volume behind the iris 9 and bounded by theciliary body 6, fiber zonules 5, and the crystalline lens 4. Thevitreous humor 10 is located between the crystalline lens 4 and theretina 11. Light entering the eye is optically focused through thecornea 3 and crystalline lens.

With reference to FIG. 2, the corneoscleral junction of the eye is theportion of the anterior chamber 7 at the intersection of the iris 9, thesclera 2, and the cornea 3. The anatomy of the eye 1 at thecorneoscleral junction includes a trabecular meshwork 12. The trabecularmeshwork 12 is a fibrous network of tissue that encircles the iris 9within the eye 1. In simplified, general terms the tissues of thecorneoscleral junction are arranged as follows: the iris 9 meets theciliary body 6, the ciliary body meets with the underside of the scleralspur 14, the top of the scleral spur serves as an attachment point forthe bottom of the trabecular meshwork 12. The ciliary body is presentmainly in the posterior chamber, but also extends into the very cornerof the anterior chamber 7. The network of tissue layers that make up thetrabecular meshwork 12 are porous and thus present a pathway for theegress of aqueous humor 8 flowing from the anterior chamber 7. Thispathway may be referred to herein as an aqueous humor outflow pathway,an aqueous outflow pathway, or simply an outflow pathway.

Referring to FIG. 3, the pathway formed by the pores in the trabecularmeshwork 12 connect to a set of thin porous tissue layers called theuveal 15, the corneoscleral meshwork 16, and the juxtacanalicular tissue17. The juxtacanalicular tissue 17, in turn, abuts a structure calledSchlemm's canal 18. The Schlemm's canal 18 carries a mixture of aqueoushumor 8 and blood from the surrounding tissue to drain into the venoussystem though a system of collector channels 19. As shown in FIG. 2, thevascular layer of the eye, referred to as the choroid 20, is next to thesclera 2. A space, called the suprachoroidal space 21, may be presentbetween the choroid 20 and the sclera 2. The general region near theperiphery of the wedge between the cornea 3 and the iris 9, runningcircumferentially is called the irido-corneal angle 13. Theirido-corneal angle 13 may also be referred to as the corneal angle ofthe eye or simply the angle of the eye. The ocular tissues illustratedin FIG. 3 are all considered to be within the irido-corneal angle 13.

With reference to FIG. 4, two possible outflow pathways for the movementof aqueous humor 8 include a trabecular outflow pathway 40 and auveoscleral outflow pathway 42. Aqueous humor 8, which is produced bythe ciliary body 6, flows from the posterior chamber 23 through thepupil into the anterior chamber 7, and then exits the eye through one ormore of the two different outflow pathways 40, 42. Approximately 90% ofthe aqueous humor 8 leaves via the trabecular outflow pathway 40 bypassing through the trabecular meshwork 12, into the Schlemm's canal 18and through one or more plexus of collector channels 19 before drainingthrough a drain path 41 into the venous system. Any remaining aqueoushumor 8 leaves primarily through the uveoscleral outflow pathway 42. Theuveoscleral outflow pathway 42 passes through the ciliary body 6 faceand iris root into the suprachoroidal space 21 (shown in FIG. 2).Aqueous humor 8 drains from the suprachoroidal space 21, from which itcan be drained through the sclera 2.

The intra-ocular pressure of the eye depends on the aqueous humor 8outflow through the trabecular outflow pathway 40 and the resistance tooutflow of aqueous humor through the trabecular outflow pathway. Theintra-ocular pressure of the eye is largely independent of the aqueoushumor 8 outflow through the uveoscleral outflow pathway 42. Resistanceto the outflow of aqueous humor 8 through the trabecular outflow pathway40 may lead to elevated intra-ocular pressure of the eye, which is awidely recognized risk factor for glaucoma. Resistance through thetrabecular outflow pathway 40 may increase due a collapsed ormalfunctioning Schlemm's canal 18 and trabecular meshwork 12.

Referring to FIG. 5, as an optical system, the eye 1 is represented byan optical model described by idealized centered and rotationallysymmetrical surfaces, entrance and exit pupils, and six cardinal points:object and image space focal points, first and second principal planes,and first and second nodal points. Angular directions relative to thehuman eye are often defined with respect to an optical axis 24, a visualaxis 26, a pupillary axis 28 and a line of sight 29 of the eye. Theoptical axis 24 is the symmetry axis, the line connecting the verticesof the idealized surfaces of the eye. The visual axis 26 connects thefoveal center 22 with the first and second nodal points to the object.The line of sight 29 connects the fovea through the exit and entrancepupils to the object. The pupillary axis 28 is normal to the anteriorsurface of the cornea 3 and directed to the center of the entrancepupil. These axes of the eye differ from one another only by a fewdegrees and fall within a range of what is generally referred to as thedirection of view.

Glaucoma

Glaucoma is a group of diseases that can harm the optic nerve and causevision loss or blindness. It is the leading cause of irreversibleblindness. Approximately 80 million people are estimated to haveglaucoma worldwide and of these, approximately 6.7 million arebilaterally blind. More than 2.7 million Americans over age 40 haveglaucoma. Symptoms start with loss of peripheral vision and can progressto blindness.

There are two forms of glaucoma, one is referred to as closed-angleglaucoma, the other as open-angled glaucoma. With reference to FIGS.1-4, in closed-angle glaucoma, the iris 9 in a collapsed anteriorchamber 7 may obstruct and close off the flow of aqueous humor 8. Inopen-angle glaucoma, which is the more common form of glaucoma, thepermeability of ocular tissue may be affected by irregularities in thejuxtacanalicular tissue 17 and inner wall of Schlemm's canal 18 a,blockage of tissue in the irido-corneal angle 13 along the trabecularoutflow pathway 40.

As previously stated, elevated intra-ocular pressure (IOP) of the eye,which damages the optic nerve, is a widely recognized risk factor forglaucoma. However, not every person with increased eye pressure willdevelop glaucoma, and glaucoma can develop without increased eyepressure. Nonetheless, it is desirable to reduce elevated TOP of the eyeto reduce the risk of glaucoma.

Methods of diagnosing conditions of the eye of a patient with glaucomainclude visual acuity tests and visual field tests, dilated eye exams,tonometry, i.e. measuring the intra-ocular pressure of the eye, andpachymetry, i.e. measuring the thickness of the cornea. Deterioration ofvision starts with the narrowing of the visual field and progresses tototal blindness. Imaging methods include slit lamp examination,observation of the irido-corneal angle with a gonioscopic lens andoptical coherence tomography (OCT) imaging of the anterior chamber andthe retina

Once diagnosed, some clinically proven treatments are available tocontrol or lower the intra-ocular pressure of the eye to slow or stopthe progress of glaucoma. The most common treatments include: 1)medications, such as eye drops or pills, 2) laser surgery, and 3)traditional surgery. Treatment usually begins with medication. However,the efficacy of medication is often hindered by patient non-compliance.When medication does not work for a patient, laser surgery is typicallythe next treatment to be tried. Traditional surgery is invasive, morehigh risk than medication and laser surgery, and has a limited timewindow of effectiveness. Traditional surgery is thus usually reserved asa last option for patients whose eye pressure cannot be controlled withmedication or laser surgery.

Laser Surgery

With reference to FIG. 2, laser surgery for glaucoma targets thetrabecular meshwork 12 to decrease aqueous humor 8 flow resistance.Common laser treatments include Argon Laser Trabeculoplasty (ALT),Selective Laser Trabeculoplasty (SLT) and Excimer Laser Trabeculostomy(ELT).

ALT was the first laser trabeculoplasty procedure. During the procedure,an argon laser of 514 nm wavelength is applied to the trabecularmeshwork 12 around 180 degrees of the circumference of the irido-cornealangle 13. The argon laser induces a thermal interaction with the oculartissue that produces openings in the trabecular meshwork 12. ALT,however, causes scarring of the ocular tissue, followed by inflammatoryresponses and tissue healing that may ultimately close the openingthrough the trabecular meshwork 12 formed by the ALT treatment, thusreducing the efficacy of the treatment. Furthermore, because of thisscarring, ALT therapy is typically not repeatable.

SLT is designed to lower the scarring effect by selectively targetingpigments in the trabecular meshwork 12 and reducing the amount of heatdelivered to surrounding ocular tissue. During the procedure, asolid-state laser of 532 nm wavelength is applied to the trabecularmeshwork 12 between 180 to 360 degrees around the circumference of theirido-corneal angle 13 to remove the pigmented cells lining thetrabeculae which comprise the trabecular meshwork. The collagenultrastructure of the trabecular meshwork is preserved during SLT. 12.SLT treatment can be repeated, but subsequent treatments have lowereffects on TOP reduction.

ELT uses a 308 nm wavelength ultraviolet (UV) excimer laser andnon-thermal interaction with ocular tissue to treat the trabecularmeshwork 12 and inner wall of Schlemm's canal in a manner that does notinvoke a healing response. Therefore, the TOP lowering effect lastslonger. However, because the UV light of the laser cannot penetrate deepinto the eye, the laser light is delivered to the trabecular meshwork 12via an optical fiber inserted into the eye 1 through an opening and thefiber is brought into contact with the trabecular meshwork. Theprocedure is highly invasive and is generally practiced simultaneouslywith cataract procedures when the eye is already surgically open. LikeALT and SLT, ELT also lacks control over the amount of IOP reduction.

None of these existing laser treatments represents an ideal treatmentfor glaucoma. Accordingly, what is needed are systems, apparatuses, andmethod for laser surgery treatment of glaucoma that effectively reduceIOP non-invasively without significant scarring of tissue, so thetreatment may be completed in a single procedure and repeated at a latertime if necessary.

SUMMARY

The present disclosure relates to a method of treating a target volumeof ocular tissue of an irido-corneal angle of an eye with a laser havinga direction of propagation toward the target volume of ocular tissue,where the target volume of ocular tissue is characterized by a distalextent, a proximal extent, and a lateral extent. The method includesinitially photodisrupting tissue at an initial depth corresponding tothe distal extent of the target volume of ocular tissue. To this end,light from a femtosecond laser is focused at a spot in the tissue at theinitial depth. Optical energy sufficient to photodisrupt the tissue isthen applied to the tissue by, for example, scanning the laser inmultiple directions defining an initial treatment plane, to therebyphotodisrupt an initial layer of tissue of the target volume.

The method also includes subsequently photodisrupting tissue at one ormore subsequent depths between the distal extent of the target volume ofocular tissue and the proximal extent of the target volume by moving afocus of the laser in a direction opposite the direction of propagationof the laser. To this end, light from a femtosecond laser is focused ata spot in the tissue at a subsequent depth. Optical energy sufficient tophotodisrupt the tissue is then applied to the tissue by, for example,scanning the laser in multiple directions defining a subsequenttreatment plane, to thereby photodisrupt a subsequent layer of tissue ofthe target volume. Photodisrupting at one or more subsequent depths isrepeated at a plurality of different subsequent depths until tissue atthe proximal extent of the target volume of ocular tissue isphotodisrupted.

In additional aspects, the method includes, after photodisrupting thetarget volume of tissue, photodisrupting tissue debris or bubblesbetween the proximal extent of the target volume of ocular tissue andthe distal extent of the target volume by moving the focus of the laserin the direction of propagation of the laser and rescanning the laser atone or more of the subsequent treatment planes and the initial treatmentplane. The method may further include, repeating the initialphotodisrupting of tissue and the subsequent photodisrupting of tissueone or more times.

The present disclosure also relates to a system for treating a targetvolume of ocular tissue of an irido-corneal angle of an eye with alaser, where the target volume of ocular tissue characterized by adistal extent, a proximal extent, and a lateral extent. The systemincludes a first optical subsystem including a focusing objectiveconfigured to be coupled to the eye, and a second optical subsystemincluding a laser source configured to output a laser beam. The secondoptical subsystem also includes a plurality of components configured toone or more of focus, scan, and direct the laser beam through thefocusing objective, in a direction of propagation toward the targetvolume of ocular tissue.

The system further includes a control system coupled to the secondoptical subsystem and configured to control the focus and scan of thelaser beam to initially photodisrupt tissue at an initial depthcorresponding to the distal extent of the target volume of oculartissue. To this end, the control system is configured to focus lightfrom a femtosecond laser at a spot in the tissue at the initial depth,and then apply optical energy to the tissue, where the energy issufficient to photodisrupt tissue. The control system controls the focusand scan of the laser beam during application of optical energy by beingfurther configured to scan the laser in multiple directions defining aninitial treatment plane, to thereby photodisrupt an initial layer oftissue of the target volume of ocular tissue.

The control system is also configured to control the focus and scan ofthe laser beam to subsequently photodisrupt tissue at one or moresubsequent depths between the distal extent of the target volume ofocular tissue and the proximal extent of the target volume by moving afocus of the laser in a direction opposite the direction of propagationof the laser. To this end, the control system is configured to focuslight from a femtosecond laser at a spot in the tissue at a subsequentdepth, and then apply optical energy to the tissue, where the energy issufficient to photodisrupt tissue. The control system controls the focusand scan of the laser beam during application of optical energy by beingfurther configured to scan the laser in multiple directions defining asubsequent treatment plane, to thereby photodisrupt a subsequent layerof tissue of the target volume of ocular tissue.

In additional aspects, the control system is configured to control thefocus and scan of the laser beam to photodisrupt tissue debris orbubbles between the proximal extent of the target volume of oculartissue and the distal extent of the target volume of ocular tissue bymoving the focus of the laser in the direction of propagation of thelaser, after photodisrupting the target volume of ocular tissue, andrescanning the laser at one or more of the subsequent treatment planesand the initial treatment plane. The control system is furtherconfigured to control the focus and scan of the laser beam to repeat theinitial photodisrupting of tissue and the subsequent photodisrupting oftissue one or more times.

The present disclosure also relates to a method of treating an eyecomprising an anterior chamber, a Schlemm's canal, and a trabecularmeshwork therebetween. The method includes initially photodisruptingocular tissue at or near an interface of an inner wall of the Schlemm'scanal and the trabecular meshwork. To this end, light from a femtosecondlaser is focused at a spot in the ocular tissue at or near the interfaceof the inner wall of the Schlemm's canal and the trabecular meshwork.Optical energy sufficient to photodisrupt the tissue is then applied tothe tissue. The method also includes subsequently photodisrupting oculartissue of the trabecular meshwork. To this end, light from a femtosecondlaser is focused at a spot in tissue of the trabecular meshwork. Opticalenergy sufficient to photodisrupt the tissue is then applied to thetissue. In additional aspects, the method includes, repeating theinitial photodisrupting of ocular tissue and the subsequentphotodisrupting of ocular tissue one or more times until an opening isformed between the anterior chamber and the Schlemm's canal.

The present disclosure also relates to a system for treating an eyecomprising an anterior chamber, a Schlemm's canal, and a trabecularmeshwork therebetween. The system includes a first optical subsystemincluding a focusing objective configured to be coupled to the eye, anda second optical subsystem including a laser source configured to outputa laser beam. The second optical subsystem further includes a pluralityof components configured to one or more of focus, scan, and direct thelaser beam through the focusing objective, toward ocular tissue.

The system also includes a control system coupled to the second opticalsubsystem and configured to control the focus and the scan of the laserbeam to initially photodisrupt ocular tissue at or near an interface ofan inner wall of the Schlemm's canal and the trabecular meshwork. Tothis end, the control system is configured to focus light from afemtosecond laser at a spot in the ocular tissue at or near theinterface of the inner wall of the Schlemm's canal and the trabecularmeshwork, and then apply optical to the tissue, where the energy issufficient to photodisrupt tissue. The control system is also configuredto control the focus and scan of the laser beam to subsequentlyphotodisrupt tissue of the trabecular meshwork. To this end, the controlsystem is configured to focus light from a femtosecond laser at a spotin tissue of the trabecular meshwork, and then apply optical energy tothe tissue, where the energy is sufficient to photodisrupt tissue. Inadditional aspects, the control system is further configured to controlthe focus and scan of the laser beam to repeat the initialphotodisrupting of ocular tissue and the subsequent photodisrupting ofocular tissue one or more times until an opening is formed between theanterior chamber and the Schlemm's canal.

It is understood that other aspects of apparatuses and methods willbecome apparent to those skilled in the art from the following detaileddescription, wherein various aspects of apparatuses and methods areshown and described by way of illustration. As will be realized, theseaspects may be implemented in other and different forms and its severaldetails are capable of modification in various other respects.Accordingly, the drawings and detailed description are to be regarded asillustrative in nature and not as restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

Various aspects of systems, apparatuses, and methods will now bepresented in the detailed description by way of example, and not by wayof limitation, with reference to the accompanying drawings, wherein:

FIG. 1 is a sectional schematic illustration of a human eye and itsinterior anatomical structures.

FIG. 2 is a sectional schematic illustration of the irido-corneal angleof the eye of FIG. 1.

FIG. 3 is a sectional schematic illustration detailing anatomicalstructures in the irido-corneal angle of FIG. 2, including thetrabecular meshwork, Schlemm's canal, and one or more collector channelsbranching from the Schlemm's canal.

FIG. 4 is a sectional schematic illustration of various outflow pathwaysfor aqueous humor through the trabecular meshwork, Schlemm's canal, andcollector channels of FIG. 3.

FIG. 5 is a sectional schematic illustration of a human eye showingvarious axes associated with the eye.

FIG. 6 is a sectional schematic illustration of an angled beam pathalong which one or more light beams may access the irido-corneal angleof the eye.

FIG. 7 is a block diagram of an integrated surgical system fornon-invasive glaucoma surgery including a control system, a femtosecondlaser source, an OCT imaging apparatus, a microscope, beam conditionersand scanners, beam combiners, a focusing objective, and a patientinterface.

FIG. 8 is a detailed block diagram of the integrated surgical system ofFIG. 7.

FIGS. 9a and 9b are schematic illustrations of the focusing objective ofthe integrated surgical system of FIG. 7 coupled to (FIG. 9a ) anddecoupled from (FIG. 9b ) the patient interface of the integratedsurgical system of FIG. 7.

FIG. 9c is a schematic illustration of components of the focusingobjective and the patient interface included in FIGS. 9a and 9 b.

FIGS. 10a and 10b are schematic illustrations of components of theintegrated surgical system of FIGS. 7 and 8 functionally arranged toform a first optical system and a second optical subsystem that enableaccess to the to the irido-corneal angle along the angled beam path ofFIG. 6.

FIG. 10c is a schematic illustration of a beam passing through the firstoptical subsystem of FIGS. 10a and 10b and into the eye.

FIG. 11 is a three-dimensional schematic illustration of anatomicalstructures in the irido-corneal angle, including the trabecularmeshwork, Schlemm's canal, a collector channel branching from theSchlemm's canal, and a surgical volume of ocular tissue to be treated bythe integrated surgical system of FIG. 7.

FIG. 12 is a two-dimensional schematic illustration of anatomicalstructures in the irido-corneal angle and a laser treatment pattern tobe applied by the integrated surgical system of FIG. 7 to affect asurgical volume of ocular tissue between the Schlemm's canal and theanterior chamber as shown in FIG. 11.

FIG. 13 is a three-dimensional schematic illustration of FIG. 11subsequent to treatment of the surgical volume of ocular tissue by alaser based on the laser treatment pattern of FIG. 12 that forms anopening between the Schlemm's canal and the anterior chamber.

FIGS. 14a and 14b are a series of schematic illustrations of a laserscanning process based on the treatment pattern of FIG. 12, where thescanning begins adjacent the anterior chamber and proceeds toward theSchlemm's canal.

FIGS. 15a-15g are a series of schematic illustrations of a laserscanning process based on the treatment pattern of FIG. 12, where thescanning begins adjacent the Schlemm's canal and proceeds toward theanterior chamber.

FIGS. 16a and 16b are a series of schematic illustrations of an optionallaser scanning process through the opening of FIG. 15g , where thescanning begins at the end of the opening adjacent the anterior chamberand proceeds toward the Schlemm's canal.

FIG. 17 is a flowchart of a method of treating a volume of oculartissue.

FIG. 18 is a flowchart of a method of treating an eye comprising ananterior chamber, a Schlemm's canal, and a trabecular meshwork.

DETAILED DESCRIPTION

Disclosed herein are systems, apparatuses, and methods for safely andeffectively reducing intra-ocular pressure (IOP) in the eye to eithertreat or reduce the risk of glaucoma. The systems, apparatuses, andmethods enable access to the irido-corneal angle of the eye andintegrate laser surgery techniques with high resolution imaging toprecisely diagnose, locate, and treat abnormal ocular tissue conditionswithin the irido-corneal angle that may be causing elevated IOP.

An integrated surgical system disclosed herein is configured to reduceintraocular pressure in an eye having a cornea, an anterior chamber, andan irido-corneal angle comprising an aqueous humor outflow pathwayformed of a trabecular meshwork, a Schlemm's canal, and one or morecollector channels branching from the Schlemm's canal. The integratedsurgical system also includes a first optical subsystem and a secondoptical subsystem. The first optical subsystem includes a windowconfigured to be coupled to the cornea and an exit lens configured to becoupled to the window. The second optical subsystem includes an opticalcoherence tomography (OCT) imaging apparatus configured to output an OCTbeam, a laser source configured to output a laser beam, and a pluralityof components, e.g., lenses and mirrors, configured to condition,combine, or direct the OCT beam and the laser beam toward the firstoptical subsystem.

The integrated surgical system also includes a control system coupled tothe OCT imaging apparatus, the laser source, and the second opticalsubsystem. The controller is configured to instruct the OCT imagingapparatus to output an OCT beam and the laser source to output a laserbeam, for delivery through the cornea, and the anterior chamber into theirido-corneal angle. In one configuration, the control system controlsthe second optical subsystem, so the OCT beam and the laser beam aredirected into the first optical subsystem along a second optical axisthat is offset from the first optical axis and that extends into theirido-corneal angle along an angled beam path 30.

Directing each of an OCT beam and a laser beam along the same secondoptical axis into the irido-corneal angle of the eye is beneficial inthat it enables direct application of the result of the evaluation ofthe condition into the treatment plan and surgery with precision in oneclinical setting. Furthermore, combining OCT imaging and laser treatmentallows targeting the ocular tissue with precision not available with anyexisting surgical systems and methods. Surgical precision afforded bythe integrated surgical system allows for the affecting of only thetargeted tissue of microscopic size and leaves the surrounding tissueintact. The microscopic size scale of the affected ocular tissue to betreated in the irido-corneal angle of the eye ranges from a fewmicrometers to a few hundred micrometers. For example, with reference toFIGS. 2 and 3, the cross-sectional size of the normal Schlemm's canal 18is an oval shape of a few tens of micrometers by a few hundredmicrometers. The diameter of collector channels 19 and veins is a fewtens of micrometers. The thickness of the juxtacanalicular tissue 17 isa few micrometers, the thickness of the trabecular meshwork 12 is arounda hundred micrometers.

The control system of the integrated surgical system is furtherconfigured to instruct the laser source to modify a volume of oculartissue within the outflow pathway to reduce a pathway resistance presentin one or more of the trabecular meshwork, the Schlemm's canal, and theone or more collector channels by applying the laser beam to oculartissue defining the volume to thereby cause photo-disruptive interactionwith the ocular tissue to reduce the pathway resistance or create a newoutflow pathway.

The laser source may be a femtosecond laser. Femtosecond lasers providenon-thermal photo-disruption interaction with ocular tissue to avoidthermal damage to surrounding tissue. Further, unlike other surgicalmethods, with femtosecond laser treatment opening surface incisionspenetrating the eye can be avoided, enabling a non-invasive treatment.Instead of performing the treatment in a sterile surgical room, thenon-invasive treatment can be performed in a non-sterile outpatientfacility.

An additional imaging component may be included the integrated surgicalsystem to provide direct visual observation of the irido-corneal anglealong an angle of visual observation. For example, a microscope orimaging camera may be included to assist the surgeon in the process ofdocking the eye to the patient interface or an immobilizing device,location of ocular tissues in the eye and observing the progress of thesurgery. The angle of visual observation can also be along the angledbeam path 30 to the irido-corneal angle 13 through the cornea 3 and theanterior chamber 7.

Images from the OCT imaging apparatus and the additional imagingcomponent providing visual observation, e.g. microscope, are combined ona display device such as a computer monitor. Different images can beregistered and overlaid on a single window, enhanced, processed,differentiated by false color for easier understanding. Certain featuresare computationally recognized by a computer processor, imagerecognition and segmentation algorithm can be enhanced, highlighted,marked for display. The geometry of the treatment plan can also becombined and registered with imaging information on the display deviceand marked up with geometrical, numerical and textual information. Thesame display can also be used for user input of numerical, textual andgeometrical nature for selecting, highlighting and marking features,inputting location information for surgical targeting by keyboard,mouse, cursor, touchscreen, audio or other user interface devices.

OCT Imaging

The main imaging component of the integrated surgical system disclosedherein is an OCT imaging apparatus. OCT technology may be used todiagnose, locate and guide laser surgery directed to the irido-cornealangle of the eye. For example, with reference to FIGS. 1-3, OCT imagingmay be used to determine the structural and geometrical conditions ofthe anterior chamber 7, to assess possible obstruction of the trabecularoutflow pathway 40 and to determine the accessibility of the oculartissue for treatment. As previously described, the iris 9 in a collapsedanterior chamber 7 may obstruct and close off the flow of aqueous humor8, resulting in closed-angle glaucoma. In open-angle glaucoma, where themacroscopic geometry of the angle is normal, the permeability of oculartissue may be affected, by blockage of tissue along the trabecularoutflow pathway 40 or by the collapse of the Schlemm's canal 18 orcollector channels 19.

OCT imaging can provide the necessary spatial resolution, tissuepenetration and contrast to resolve microscopic details of oculartissue. When scanned, OCT imaging can provide two-dimensional (2D)cross-sectional images of the ocular tissue. As another aspect of theintegrated surgical system, 2D cross-sectional images may be processedand analyzed to determine the size, shape and location of structures inthe eye for surgical targeting. It is also possible to reconstructthree-dimensional (3D) images from a multitude of 2D cross-sectionalimages but often it is not necessary. Acquiring, analyzing anddisplaying 2D images is faster and can still provide all informationnecessary for precise surgical targeting.

OCT is an imaging modality capable of providing high resolution imagesof materials and tissue. Imaging is based on reconstructing spatialinformation of the sample from spectral information of scattered lightfrom within the sample. Spectral information is extracted by using aninterferometric method to compare the spectrum of light entering thesample with the spectrum of light scattered from the sample. Spectralinformation along the direction that light is propagating within thesample is then converted to spatial information along the same axis viathe Fourier transform. Information lateral to the OCT beam propagationis usually collected by scanning the beam laterally and repeated axialprobing during the scan. 2D and 3D images of the samples can be acquiredthis way. Image acquisition is faster when the interferometer is notmechanically scanned in a time domain OCT, but interference from a broadspectrum of light is recorded simultaneously, this implementation iscalled a spectral domain OCT. Faster image acquisition may also beobtained by scanning the wavelength of light rapidly from a wavelengthscanning laser in an arrangement called a swept-source OCT.

The axial spatial resolution limit of the OCT is inversely proportionalto the bandwidth of the probing light used. Both spectral domain andswept source OCTs are capable of axial spatial resolution below 5micrometers (pa) with sufficiently broad bandwidth of 100 nanometers(nm) or more. In the spectral domain OCT, the spectral interferencepattern is recorded simultaneously on a multichannel detector, such as acharge coupled device (CCD) or complementary metal oxide semiconductor(CMOS) camera, while in the swept source OCT the interference pattern isrecorded in sequential time steps with a fast optical detector andelectronic digitizer. There is some acquisition speed advantage of theswept source OCT but both types of systems are evolving and improvingrapidly, and resolution and speed is sufficient for purposes of theintegrated surgical system disclosed herein. Stand-alone OCT systems andOEM components are now commercially available from multiple vendors,such as Optovue Inc., Fremont, Calif., Topcon Medical Systems, Oakland,N.J., Carl Zeiss Meditec AG, Germany, Nidek, Aichi, Japan, Thorlabs,Newton, N.J., Santec, Aichi, Japan, Axsun, Billercia, Mass., and othervendors.

Femtosecond Laser Source

The preferred surgical component of the integrated surgical systemdisclosed herein is a femtosecond laser. A femtosecond laser provideshighly localized, non-thermal photo-disruptive laser-tissue interactionwith minimal collateral damage to surrounding ocular tissue.Photo-disruptive interaction of the laser is utilized in opticallytransparent tissue. The principal mechanism of laser energy depositioninto the ocular tissue is not by absorption but by a highly nonlinearmultiphoton process. This process is effective only at the focus of thepulsed laser where the peak intensity is high. Regions where the beam istraversed but not at the focus are not affected by the laser. Therefore,the interaction region with the ocular tissue is highly localized bothtransversally and axially along the laser beam. The process can also beused in weakly absorbing or weakly scattering tissue. While femtosecondlasers with photo-disruptive interactions have been successfully used inophthalmic surgical systems and commercialized in other ophthalmic laserprocedures, none have been used in an integrated surgical system thataccesses the irido-corneal angle.

In known refractive procedures, femtosecond lasers are used to createcorneal flaps, pockets, tunnels, arcuate incisions, lenticule shapedincisions, partial or fully penetrating corneal incisions forkeratoplasty. For cataract procedures the laser creates a circular cuton the capsular bag of the eye for capsulotomy and incisions of variouspatterns in the lens for braking up the interior of the crystalline lensto smaller fragments to facilitate extraction. Entry incisions throughthe cornea opens the eye for access with manual surgical devices and forinsertions of phacoemulsification devices and intra-ocular lensinsertion devices. Several companies have commercialized such surgicalsystems, among them the IntraLase system now available from Johnson &Johnson Vision, Santa Ana, Calif., The LenSx and WaveLight systems fromAlcon, Fort Worth, Tex., other surgical systems from Bausch and Lomb,Rochester, N.Y., Carl Zeiss Meditec AG, Germany, Ziemer, Port,Switzerland, and LENSAR, Orlando, Fla.

These existing systems are developed for their specific applications,for surgery in the cornea, and the crystalline lens and its capsular bagand are not capable of performing surgery in the irido-corneal angle 13for several reasons. First, the irido-corneal angle 13 is not accessiblewith these surgical laser systems because the irido-corneal angle is toofar out in the periphery and is outside of surgical range of thesesystems. Second, the angle of the laser beam from these systems, whichis along the optical axis 24 to the eye 1, is not appropriate toreaching the irido-corneal angle 13, where there is significantscattering and optical distortion at the applied wavelength. Third, anyimaging capabilities these systems may have do not have theaccessibility, penetration depth and resolution to image the tissuealong the trabecular outflow pathway 40 with sufficient detail andcontrast.

In accordance with the integrated surgical system disclosed herein,clear access to the irido-corneal angle 13 is provided along the angledbeam path 30. The tissue, e.g., cornea 3 and the aqueous humor 8 in theanterior chamber 7, along this angled beam path 30 is transparent forwavelengths from approximately 400 nm to 2500 nm and femtosecond lasersoperating in this region can be used. Such mode locked lasers work attheir fundamental wavelength with Titanium, Neodymium or Ytterbiumactive material. Non-linear frequency conversion techniques known in theart, frequency doubling, tripling, sum and difference frequency mixingtechniques, optical parametric conversion can convert the fundamentalwavelength of these lasers to practically any wavelength in the abovementioned transparent wavelength range of the cornea.

Existing ophthalmic surgical systems apply lasers with pulse durationslonger than 1 ns have higher photo-disruption threshold energy, requirehigher pulse energy and the dimension of the photo-disruptiveinteraction region is larger, resulting in loss of precision of thesurgical treatment. When treating the irido-corneal angle 13, however,higher surgical precision is required. To this end, the integratedsurgical system may be configured to apply lasers with pulse durationsfrom 10 femtosecond (fs) to 1 nanosecond (ns) for generatingphoto-disruptive interaction of the laser beam with ocular tissue in theirido-corneal angle 13. While lasers with pulse durations shorter than10 fs are available, such laser sources are more complex and moreexpensive. Lasers with the described desirable characteristics, e.g.,pulse durations from 10 femtosecond (fs) to 1 nanosecond (ns), arecommercially available from multiple vendors, such as Newport, Irvine,Calif., Coherent, Santa Clara, Calif., Amplitude Systems, Pessac,France, NKT Photonics, Birkerod, Denmark, and other vendors.

Accessing the Irido-corneal Angle

An important feature afforded by the integrated surgical system isaccess to the targeted ocular tissue in the irido-corneal angle 13. Withreference to FIG. 6, the irido-corneal angle 13 of the eye may beaccessed via the integrated surgical system along an angled beam path 30passing through the cornea 3 and through the aqueous humor 8 in theanterior chamber 7. For example, one or more of an imaging beam, e.g.,an OCT beam and/or a visual observation beam, and a laser beam mayaccess the irido-corneal angle 13 of the eye along the angled beam path30.

An optical system disclosed herein is configured to direct a light beamto an irido-corneal angle 13 of an eye along an angled beam path 30. Theoptical system includes a first optical subsystem and a second opticalsubsystem. The first optical subsystem includes a window formed of amaterial with a refractive index n_(w) and has opposed concave andconvex surfaces. The first optical subsystem also includes an exit lensformed of a material having a refractive index n_(x). The exit lens alsohas opposed concave and convex surfaces. The concave surface of the exitlens is configured to couple to the convex surface of the window todefine a first optical axis extending through the window and the exitlens. The concave surface of the window is configured to detachablycouple to a cornea of the eye with a refractive index n_(c) such that,when coupled to the eye, the first optical axis is generally alignedwith the direction of view of the eye.

The second optical subsystem is configured to output a light beam, e.g.,an OCT beam or a laser beam. The optical system is configured so thatthe light beam is directed to be incident at the convex surface of theexit lens along a second optical axis at an angle α that is offset fromthe first optical axis. The respective geometries and respectiverefractive indices n_(x), and n_(w) of the exit lens and window areconfigured to compensate for refraction and distortion of the light beamby bending the light beam so that it is directed through the cornea 3 ofthe eye toward the irido-corneal angle 13. More specifically, the firstoptical system bends the light beam to that the light beam exits thefirst optical subsystem and enters the cornea 3 at an appropriate angleso that the light beam progresses through the cornea and the aqueoushumor 8 in a direction along the angled beam path 30 toward theirido-corneal angle 13.

Accessing the irido-corneal angle 13 along the angled beam path 30provides several advantages. An advantage of this angled beam path 30 tothe irido-corneal angle 13 is that the OCT beam and laser beam passesthrough mostly clear tissue, e.g., the cornea 3 and the aqueous humor 8in the anterior chamber 7. Thus, scattering of these beams by tissue isnot significant. With respect to OCT imaging, this enables the use ofshorter wavelength, less than approximately 1 micrometer, for the OCT toachieve higher spatial resolution. An additional advantage of the angledbeam path 30 to the irido-corneal angle 13 through the cornea 3 and theanterior chamber 7 is the avoidance of direct laser beam or OCT beamlight illuminating the retina 11. As a result, higher average powerlaser light and OCT light can be used for imaging and surgery, resultingin faster procedures and less tissue movement during the procedure.

Another important feature provided by the integrated surgical system isaccess to the targeted ocular tissue in the irido-corneal angle 13 in away that reduces beam discontinuity. To this end, the window and exitlens components of the first optical subsystem are configured to reducethe discontinuity of the optical refractive index between the cornea 3and the neighboring material and facilitate entering light through thecornea at a steep angle.

Having thus generally described the integrated surgical system and someof its features and advantages, a more detailed description of thesystem and its component parts follows.

Integrated Surgical System

With reference to FIG. 7, an integrated surgical system 1000 fornon-invasive glaucoma surgery includes a control system 100, a surgicalcomponent 200, a first imaging component 300 and an optional secondimaging component 400. In the embodiment of FIG. 7, the surgicalcomponent 200 is a femtosecond laser source, the first imaging component300 is an OCT imaging apparatus, and the optional second imagingcomponent 400 is a visual observation apparatus, e.g., a microscope, fordirect viewing or viewing with a camera. Other components of theintegrated surgical system 1000 include beam conditioners and scanners500, beam combiners 600, a focusing objective 700, and a patientinterface 800.

The control system 100 may be a single computer or and plurality ofinterconnected computers configured to control the hardware and softwarecomponents of the other components of the integrated surgical system1000. A user interface 110 of the control system 100 acceptsinstructions from a user and displays information for observation by theuser. Input information and commands from the user include but are notlimited to system commands, motion controls for docking the patient'seye to the system, selection of pre-programmed or live generatedsurgical plans, navigating through menu choices, setting of surgicalparameters, responses to system messages, determining and acceptance ofsurgical plans and commands to execute the surgical plan. Outputs fromthe system towards the user includes but are not limited to display ofsystem parameters and messages, display of images of the eye, graphical,numerical and textual display of the surgical plan and the progress ofthe surgery.

The control system 100 is connected to the other components 200, 300,400, 500 of the integrated surgical system 1000. Control signals fromthe control system 100 to the femtosecond laser source 200 function tocontrol internal and external operation parameters of the laser source,including for example, power, repetition rate and beam shutter. Controlsignals from the control system 100 to the OCT imaging apparatus 300function to control OCT beam scanning parameters, and the acquiring,analyzing and displaying of OCT images.

Laser beams 201 from the femtosecond laser source 200 and OCT beams 301from the OCT imaging apparatus 300 are directed towards a unit of beamconditioners and scanners 500. Different kind of scanners can be usedfor the purpose of scanning the laser beam 201 and the OCT beam 301. Forscanning transversal to a beam 201, 301, angular scanning galvanometerscanners are available for example from Cambridge Technology, Bedford,Mass., Scanlab, Munich, Germany. To optimize scanning speed, the scannermirrors are typically sized to the smallest size, which still supportthe required scanning angles and numerical apertures of the beams at thetarget locations. The ideal beam size at the scanners is typicallydifferent from the beam size of the laser beam 201 or the OCT beam 301,and different from what is needed at the entrance of a focusingobjective 700. Therefore, beam conditioners are applied before, after orin between individual scanners. The beam conditioner and scanners 500includes scanners for scanning the beam transversally and axially. Axialscanning changes the depth of the focus at the target region. Axialscanning can be performed by moving a lens axially in the beam path witha servo or stepper motor.

The laser beam 201 and the OCT beam 301 are combined with dichroic,polarization or other kind of beam combiners 600 to reach a commontarget volume or surgical volume in the eye. In an integrated surgicalsystem 1000 having a femtosecond laser source 200, an OCT imagingapparatus 300, and a visual observation device 400, the individual beams201, 301, 401 for each of these components may be individually optimizedand may be collinear or non-collinear to one another. The beam combiner600 uses dichroic or polarization beam splitters to split and recombinelight with different wavelength and/or polarization. The beam combiner600 may also include optics to change certain parameters of theindividual beams 201, 301, 401 such as beam size, beam angle anddivergence. Integrated visual illumination, observation or imagingdevices assist the surgeon in docking the eye to the system andidentifying surgical locations.

To resolve ocular tissue structures of the eye in sufficient detail, theimaging components 300, 400 of the integrated surgical system 1000 mayprovide an OCT beam and a visual observation beam having a spatialresolution of several micrometers. The resolution of the OCT beam is thespatial dimension of the smallest feature that can be recognized in theOCT image. It is determined mostly by the wavelength and the spectralbandwidth of the OCT source, the quality of the optics delivering theOCT beam to the target location in the eye, the numerical aperture ofthe OCT beam and the spatial resolution of the OCT imaging apparatus atthe target location. In one embodiment, the OCT beam of the integratedsurgical system has a resolution of no more than 5 μm.

Likewise, the surgical laser beam provided by the femtosecond lasersource 200 may be delivered to targeted locations with severalmicrometer accuracy. The resolution of the laser beam is the spatialdimension of the smallest feature at the target location that can bemodified by the laser beam without significantly affecting surroundingocular tissue. It is determined mostly by the wavelength of the laserbeam, the quality of the optics delivering the laser beam to targetlocation in the eye, the numerical aperture of the laser beam, theenergy of the laser pulses in the laser beam and the spatial resolutionof the laser scanning system at the target location. In addition, tominimize the threshold energy of the laser for photo-disruptiveinteraction, the size of the laser spot should be no more thanapproximately 5 μm.

It should be noted that, while the visual observation beam 401 isacquired by the visual observation device 400 using fixed, non-scanningoptics, the OCT beam 301 of the OCT imaging apparatus 300 is scannedlaterally in two transversal directions. The laser beam 201 of thefemtosecond laser source 200 is scanned in two lateral dimensions andthe depth of the focus is scanned axially.

For practical embodiments, beam conditioning, scanning and combining theoptical paths are certain functions performed on the laser, OCT andvisual observation optical beams. Implementation of those functions mayhappen in a different order than what is indicated in FIG. 7. Specificoptical hardware that manipulates the beams to implement those functionscan have multiple arrangements with regards to how the optical hardwareis arranged. They can be arranged in a way that they manipulateindividual optical beams separately, in another embodiment one componentmay combine functions and manipulates different beams. For example, asingle set of scanners can scan both the laser beam 201 and the OCT beam301. In this case, separate beam conditioners set the beam parametersfor the laser beam 201 and the OCT beam 301, then a beam combinercombines the two beams for a single set of scanners to scan the beams.While many combinations of optical hardware arrangements are possiblefor the integrated surgical system, the following section describes indetail an example arrangement.

Beam Delivery

In the following description, the term beam may—depending on thecontext—refer to one of a laser beam, an OCT beam, or a visualobservation beam. A combined beam refers to two or more of a laser beam,an OCT beam, or a visual observation beam that are either collinearlycombined or non-collinearly combined. Example combined beams include acombined OCT/laser beam, which is a collinear or non-colinearcombination of an OCT beam and a laser beam, and a combinedOCT/laser/visual beam, which is a collinear or non-collinear combinationof an OCT beam, a laser beam, and a visual beam. In a collinearlycombined beam, the different beams may be combined by dichroic orpolarization beam splitters, and delivered along a same optical paththrough a multiplexed delivery of the different beams. In anon-collinear combined beam, the different beams are delivered at thesame time along different optical paths that are separated spatially orby an angle between them. In the description to follow, any of theforegoing beams or combined beams may be generically referred to as alight beam. The terms distal and proximal may be used to designate thedirection of travel of a beam, or the physical location of componentsrelative to each other within the integrated surgical system. The distaldirection refers to a direction toward the eye; thus an OCT beam outputby the OCT imaging apparatus moves in the distal direction toward theeye. The proximal direction refers to a direction away from the eye;thus an OCT return beam from the eye moves in the proximal directiontoward the OCT imaging apparatus.

Referring to FIG. 8, an example integrated surgical system is configuredto deliver each of a laser beam 201 and an OCT beam 301 in the distaldirection toward an eye 1, and receive each of an OCT return beam andthe visual observation beam 401 back from the eye 1. Regarding thedelivery of a laser beam, a laser beam 201 output by the femtosecondlaser source 200 passes through a beam conditioner 510 where the basicbeam parameters, beam size, divergence are set. The beam conditioner 510may also include additional functions, setting the beam power or pulseenergy and shutter the beam to turn it on or off. After existing thebeam conditioner 510, the laser beam 210 enters an axial scanning lens520. The axial scanning lens 520, which may include a single lens or agroup of lenses, is movable in the axial direction 522 by a servo motor,stepper motor or other control mechanism. Movement of the axial scanninglens 520 in the axial direction 522 changes the axial distance of thefocus of the laser beam 210 at a focal point.

In accordance with a particular embodiment of the integrated surgicalsystem, an intermediate focal point 722 is set to fall within, and isscannable in, the conjugate surgical volume 721, which is an imageconjugate of the surgical volume 720, determined by the focusingobjective 700. The surgical volume 720 is the spatial extent of theregion of interest within the eye where imaging and surgery isperformed. For glaucoma surgery, the surgical volume 720 is the vicinityof the irido-corneal angle 13 of the eye.

A pair of transverse scanning mirrors 530, 532 rotated by a galvanometerscanner scan the laser beam 201 in two essentially orthogonaltransversal directions, e.g., in the x and y directions. Then the laserbeam 201 is directed towards a dichroic or polarization beam splitter540 where it is reflected toward a beam combining mirror 601 configuredto combine the laser beam 201 with an OCT beam 301.

Regarding delivery of an OCT beam, an OCT beam 301 output by the OCTimaging apparatus 300 passes through a beam conditioner 511, an axiallymoveable focusing lens 521 and a transversal scanner with scanningmirrors 531 and 533. The focusing lens 521 is used set the focalposition of the OCT beam in the conjugate surgical volume 721 and thereal surgical volume 720. The focusing lens 521 is not scanned forobtaining an OCT axial scan. Axial spatial information of the OCT imageis obtained by Fourier transforming the spectrum of theinterferometrically recombined OCT return beam 301 and reference beams302. However, the focusing lens 521 can be used to re-adjust the focuswhen the surgical volume 720 is divided into several axial segments.This way the optimal imaging spatial resolution of the OCT image can beextended beyond the Rayleigh range of the OCT signal beam, at theexpense of time spent on scanning at multiple ranges.

Proceeding in the distal direction toward the eye 1, after the scanningmirrors 531 and 533, the OCT beam 301 is combined with the laser beam201 by the beam combiner mirror 601. The OCT beam 301 and laser beam 201components of the combined laser/OCT beam 550 are multiplexed and travelin the same direction to be focused at an intermediate focal point 722within the conjugate surgical volume 721. After having been focused inthe conjugate surgical volume 721, the combined laser/OCT beam 550propagates to a second beam combining mirror 602 where it is combinedwith a visual observation beam 401 to form a combined laser/OCT/visualbeam 701.

The combined laser/OCT/visual beam 701 traveling in the distal directionthen passes through the focusing objective 700, and a window 801 of apatient interface, where the intermediate focal point 722 of the laserbeam within the conjugate surgical volume 721 is re-imaged into a focalpoint in the surgical volume 720. The focusing objective 700 re-imagesthe intermediate focal point 722, through the window 801 of a patientinterface, into the ocular tissue within the surgical volume 720.

A scattered OCT return beam 301 from the ocular tissue travels in theproximal direction to return to the OCT imaging apparatus 300 along thesame paths just described, in reverse order. The reference beam 302 ofthe OCT imaging apparatus 300, passes through a reference delay opticalpath and return to the OCT imaging apparatus from a moveable mirror 330.The reference beam 302 is combined interferometrically with the OCTreturn beam 301 on its return within the OCT imaging apparatus 300. Theamount of delay in the reference delay optical path is adjustable bymoving the moveable mirror 330 to equalize the optical paths of the OCTreturn beam 301 and the reference beam 302. For best axial OCTresolution, the OCT return beam 301 and the reference beam 302 are alsodispersion compensated to equalize the group velocity dispersion withinthe two arms of the OCT interferometer.

When the combined laser/OCT/visual beam 701 is delivered through thecornea 3 and the anterior chamber 7, the combined beam passes throughposterior and anterior surface of the cornea at a steep angle, far fromnormal incidence. These surfaces in the path of the combinedlaser/OCT/visual beam 701 create excessive astigmatism and comaaberrations that need to be compensated for.

With reference to FIGS. 9a and 9b , in an embodiment of the integratedsurgical system 1000, optical components of the focusing objective 700and patient interface 800 are configured to minimize spatial andchromatic aberrations and spatial and chromatic distortions. FIG. 9ashows a configuration when both the eye 1, the patient interface 800 andthe focusing objective 700 all coupled together. FIG. 9b shows aconfiguration when both the eye 1, the patient interface 800 and thefocusing objective 700 all detached from one another.

The patient interface 800 optically and physically couples the eye 1 tothe focusing objective 700, which in turn optically couples with otheroptic components of the integrated surgical system 1000. The patientinterface 800 serves multiple functions. It immobilizes the eye relativeto components of the integrated surgical system; creates a sterilebarrier between the components and the patient; and provides opticalaccess between the eye and the instrument. The patient interface 800 isa sterile, single use disposable device and it is coupled detachably tothe eye 1 and to the focusing objective 700 of the integrated surgicalsystem 1000.

The patient interface 800 includes a window 801 having an eye-facing,concave surface 812 and an objective-facing, convex surface 813 oppositethe concave surface. The window 801 thus has a meniscus form. Withreference to FIG. 9c , the concave surface 812 is characterized by aradius of curvature r_(e), while the convex surface 813 is characterizedby a radius of curvature r_(w). The concave surface 812 is configured tocouple to the eye, either through a direct contact or through indexmatching material, liquid or gel, placed in between the concave surface812 and the eye 1. The window 801 may be formed of glass and has arefractive index n_(w). In one embodiment, the window 801 is formed offused silica and has a refractive index n_(w) of 1.45. Fused silica hasthe lowest index from common inexpensive glasses. Fluoropolymers such asthe Teflon AF are another class of low index materials that haverefractive indices lower than fused silica, but their optical quality isinferior to glasses and they are relatively expensive for high volumeproduction. In another embodiment the window 801 is formed of the commonglass BK7 and has a refractive index n_(w) of 1.50. A radiationresistant version of this glass, BK7G18 from Schott AG, Mainz, Germany,allows gamma sterilization of the patient interface 800 without thegamma radiation altering the optical properties of the window 801.

Returning to FIGS. 9a and 9b , the window 801 is surrounded by a wall803 of the patient interface 800 and an immobilization device, such as asuction ring 804. When the suction ring 804 is in contact with the eye1, an annular cavity 805 is formed between the suction ring and the eye.When vacuum applied to the suction ring 804 and the cavity via a vacuumtube a vacuum pump (not shown in FIGS. 9a and 9b ), vacuum forcesbetween the eye and the suction ring attach the eye to the patientinterface 800 during surgery. Removing the vacuum releases or detach theeye 1.

The end of the patient interface 800 opposite the eye 1 includes anattachment interface 806 configured to attach to the housing 702 of thefocusing objective 700 to thereby affix the position of the eye relativeto the other components of the integrated surgical system 1000. Theattachment interface 806 can work with mechanical, vacuum, magnetic orother principles and it is also detachable from the integrated surgicalsystem.

The focusing objective 700 includes an aspheric exit lens 710 having aneye-facing, concave surface 711 and a convex surface 712 opposite theconcave surface. The exit lens 710 thus has a meniscus form. While theexit lens 710 shown in FIGS. 9a and 9b is an aspheric lens giving moredesign freedom, in other configurations the exit lens may be a sphericallens. Alternatively, constructing the exit lens 710 as a compound lens,as opposed to a singlet, allows more design freedom to optimize theoptics while preserving the main characteristics of the optical systemas presented here. With reference to FIG. 9c , the concave surface 711is characterized by a radius of curvature r_(y), while the convexsurface 712 is characterized by an aspheric shape. The aspheric convexsurface 712 in combination with the spherical concave surface 711 resultin an exit lens 710 having varying thickness, with the outer perimeteredges 715 of the lens being thinner than the central, apex region 717 ofthe lens. The concave surface 711 is configured to couple to the convexsurface 813 of the window 801. In one embodiment, the exit lens 710 isformed of fused silica and has a refractive index n_(x) of 1.45.

FIGS. 10a and 10b are schematic illustrations of components of theintegrated surgical system of FIGS. 7 and 8 functionally arranged toform an optical system 1010 having a first optical subsystem 1001 and asecond optical subsystem 1002 that enable access to a surgical volume720 in the irido-corneal angle. Each of FIGS. 10a and 10b includecomponents of the focusing objective 700 and the patient interface 800of FIG. 9a . However, for simplicity, the entirety of the focusingobjective and the patient interface are not included in FIGS. 10a and10b . Also, for additional simplicity in FIG. 10a , the planarbeam-folding mirror 740 of FIGS. 9a and 9b is not included and thecombined laser/OCT/visual beam 701 shown in FIG. 9a is unfolded orstraightened out. It is understood by those skilled in the art thatadding or removing planar beam folding mirrors does not alter theprincipal working of the optical system formed by the first opticalsubsystem and the second optical subsystem. FIG. 10c is a schematicillustration of a beam passing through the first optical subsystem ofFIGS. 10a and 10 b.

With reference to FIG. 10a , a first optical subsystem 1001 of theintegrated surgical system 1000 includes the exit lens 710 of a focusingobjective 700 and the window 801 of a patient interface 800. The exitlens 710 and the window 801 are arranged relative to each other todefine a first optical axis 705. The first optical subsystem 1001 isconfigured to receive a beam, e.g., a combined laser/OCT/visual beam701, incident at the convex surface 712 of the exit lens 710 along asecond optical axis 706, and to direct the beam toward a surgical volume720 in the irido-corneal angle 13 of the eye.

During a surgical procedure, the first optical subsystem 1001 may beassembled by interfacing the convex surface 813 of the window 801 withthe concave surface 711 of the exit lens 710. To this end, a focusingobjective 700 is docked together with a patient interface 800. As aresult, the concave surface 711 of the exit lens 710 is coupled to theconvex surface 813 of the window 801. The coupling may be by directcontact or through a layer of index matching fluid. For example, whendocking the patient interface 800 to focusing objective 700, a drop ofindex matching fluid can be applied between the contacting surfaces toeliminate any air gap that may be between the two surfaces 711, 813 tothereby help pass the combined laser/OCT/visual beam 701 through the gapwith minimal Fresnel reflection and distortion.

In order to direct the beam toward the surgical volume 720 in theirido-corneal angle 13 of the eye, the first optical subsystem 1001 isdesigned to account for refraction of the beam 701 as it passes throughthe exit lens 710, the window 801 and the cornea 3. To this end, andwith reference to FIG. 10c , the refractive index n_(x) of the exit lens710 and the refractive index n_(w) of the window 801 are selected inview of the refractive index n_(c) of the cornea 3 to cause appropriatebeam bending through the first optical subsystem 1001 so that when thebeam 701 exits the subsystem and passes through the cornea 3, the beampath is generally aligned to fall within the irido-corneal angle 13.

Continuing with reference to FIG. 10c and beginning with the interfacebetween the window 801 and the cornea 3. Too steep of an angle ofincidence at the interface where the combined laser/OCT/visual beam 701exits the window 801 and enters the cornea 3, i.e., at the interfacebetween the concave surface 812 of the window and the convex surface ofthe cornea 3, can create excessive refraction and distortion. Tominimize refraction and distortion at this interface, in one embodimentof the first optical subsystem 1001, the refractive index of the window801 is closely matched to the index of the cornea 3. For example, asdescribe above with reference to FIGS. 9a and 9b , the window 801 mayhave a refractive index lower than 1.42 to closely match the cornea 3,which has a refractive index of 1.36.

Excessive refraction and distortion at the interface where the combinedlaser/OCT/visual beam 701 exits the window 801 and enters the cornea 3may be further compensated for by controlling the bending of the beam701 as it passed through the exit lens 710 and the window 801. To thisend, in one embodiment of the first optical subsystem 1001 the index ofrefraction n_(w) of the window 801 is larger than each of the index ofrefraction n_(x) of the exit lens 710 and the index of refraction n_(c)of the cornea 3. As a result, at the interface where the combinedlaser/OCT/visual beam 701 exits the exit lens 710 and enters the window801, i.e., interface between the concave surface 711 of the exit lensand the convex surface 813 of the window, the beam passes through arefractive index change from high to low that cause the beam to bend ina first direction. Then, at the interface where the combinedlaser/OCT/visual beam 701 exits the window 801 and enters the cornea 3,i.e., interface between the concave surface 812 of the exit lens and theconvex surface of the cornea, the beam passes through a refractive indexchange from low to high that cause the beam to bend in a seconddirection opposite the first direction.

The shape of the window 801 is chosen to be a meniscus lens. As such,the incidence angle of light has similar values on both surfaces 812,813 of the window 801. The overall effect is that at the convex surface813 the light bends away from the surface normal and at the concavesurface 812 the light bends towards the surface normal. The effect islike when light passes through a plan parallel plate. Refraction on onesurface of the plate is compensated by refraction on the other surface alight passing through the plate does not change its direction.Refraction at the entering, convex surface 712 of the exit lens 710distal to the eye is minimized by setting the curvature of the enteringsurface such that angle of incidence β of light 701 at the enteringsurface is close to a surface normal 707 to the entering surface at theintersection point 708.

Here, the exit lens 710, the window 801, and the eye 1 are arranged asan axially symmetric system with a first optical axis 705. In practice,axial symmetry is an approximation because of manufacturing andalignment inaccuracies of the optical components, the natural deviationfrom symmetry of the eye and the inaccuracy of the alignment of the eyerelative to the window 801 and the exit lens 710 in a clinical setting.But, for design and practical purposes the eye 1, the window 801, andthe exit lens 710 are considered as an axially symmetric first opticalsubsystem 1001.

With continued reference to FIG. 10a , a second optical subsystem 1002is optically coupled to the first optical subsystem 1001 at an angle αrelative to the first optical axis 705 of the first optical subsystem1001. The advantage of this arrangement is that the both opticalsubsystems 1001, 1002 can be designed at a much lower numerical aperturecompared to a system where all optical components are designed on axiswith a common optical axis.

The second optical subsystem 1002 includes a relay lens 750 that, aspreviously described with reference to FIG. 8, generates a conjugatesurgical volume 721 of the surgical volume 720 within the eye. Thesecond optical subsystem 1002 includes various other componentscollectively indicated as an optical subsystem step 1003. Referring toFIG. 8, these components may include a femtosecond laser source 200, anOCT imaging apparatus 300, a visual observation device 400, beamconditioners and scanners 500, and beam combiners 600.

The second optical subsystem 1002 may include mechanical parts (notshown) configured to rotate the entire subsystem around the firstoptical axis 705 of the first optical subsystem 1001. This allowsoptical access to the whole 360-degree circumference of theirido-corneal angle 13 of the eye 1.

With reference to FIG. 10b , flexibility in arranging the first andsecond optical subsystems 1001, 1002, relative to each other may beprovided by an optical assembly 1004 interposed between the opticaloutput of the second optical subsystem 1002 and the optical input of thefirst optical subsystem 1001. In one embodiment, the optical assembly1004 may include one or more planar beam-folding mirrors 740, prisms(not shown) or optical gratings (not shown) configured to receive theoptical output, e.g., combined laser/OCT/visual beam 701, of the secondoptical subsystem 1002, change or adjust the direction of the combinedlaser/OCT/visual beam, and direct the beam to the optical input of thefirst optical subsystem 1001 while preserving the angle α between thefirst optical axis 705 and the second optical axis 706.

In another configuration, the optical assembly 1004 of planarbeam-folding mirrors 740 further includes mechanical parts (not shown)configured to rotate the assembly around the first optical axis 705 ofthe first optical subsystem 1001 while keeping the second opticalsubsystem 1002 stationary. Accordingly, the second optical axis 706 ofthe second optical subsystem 1002 can be rotated around the firstoptical axis 705 of the first optical subsystem 1001. This allowsoptical access to the whole 360-degree circumference of theirido-corneal angle 13 of the eye 1.

With considerations described above with reference to FIGS. 9a, 9b and9c , the design of the first optical subsystem 1001 is optimized forangled optical access at an angle α relative to the first optical axis705 of the first optical subsystem 1001. Optical access at the angle αcompensates for optical aberrations of the first optical subsystem 1001.Table 1 shows the result of the optimization at access angle α=72degrees with Zemax optical design software package. This design is apractical embodiment for image guided femtosecond glaucoma surgery.

TABLE 1 Center Structure and Refractive Radius Thickness SurfaceMaterial index [mm] [mm] concave Exit lens 710 of 1.45 −10 4.5 surfacefocusing objective. 711, Fused silica convex surface 712 concave Window801 of 1.50 −0.9 1.0 surface patient interface. 812, BK7G18 convexsurface 813 3 Cornea 1.36 −7.83 0.54 8 Aqueous humor 1.32 −6.53 3.5Target Ophthalmic tissue 1.38 N/A 0 to 1 mm

This design produces diffraction limited focusing of 1030 nm wavelengthlaser beams and 850 nm wavelength OCT beams with numerical aperture (NA)up to 0.2. In one design, the optical aberrations of the first opticalsubsystem are compensated to a degree that the Strehl ratio of the firstoptical subsystem for a beam with numerical aperture larger than 0.15 atthe irido-corneal angle is larger than 0.9. In another design, theoptical aberrations of the first optical subsystem are partiallycompensated, the remaining uncompensated aberrations of the firstoptical system are compensated by the second optical subsystem to adegree that the Strehl ratio of the combined first and second opticalsubsystem for a beam with numerical aperture larger than 0.15 at theirido-corneal angle is larger than 0.9.

Calibration

The femtosecond laser source 200, OCT imaging apparatus 300, and visualobservation device 400 of the integrated surgical system 1000 are firstindividually calibrated to ensure their internal integrity and thencross-calibrated for system integrity. The essential part of systemcalibration is to ensure that the when the surgical focus of a laserbeam 201 is commanded to a location of a surgical volume 720, asidentified by the OCT imaging apparatus and/or the visual observationdevice 400, the achieved location of the focus matches the commandedlocation of the focus within a certain tolerance, typically within 5 to10 μm. Also, graphical and cursor outputs, images, overlays displayed ona user interface 110, such as a computer monitor, and user inputs ofocular tissue surgical volume 720 locations accepted from the userinterface 110 should correspond to actual locations in tissue withinpredetermined tolerances of similar accuracy.

One embodiment of this spatial calibration procedure starts with imagingcalibrated scales and scaling magnifications of the OCT imagingapparatus 300 and/or the visual observation device 400 and theirdisplays in a way that the scale value on the display matches the realscale of the calibration target. Then laser calibration patters areexposed or burned into transparent calibration targets, and thecalibration patterns are subsequently imaged. Then, the intendedpatterns and the actual burned patterns are compared with the imagingsystem of the integrated surgical system 1000 or by a separatemicroscope. If they do not match within the specified tolerance, thescaling parameters of the surgical patterns are re-scaled by adjustingthe scaling of the laser beam scanners. This procedure is iterated, ifnecessary, until all spatial calibrations are within tolerance.

Minimally Invasive Surgical Treatments

FIG. 11 is a three-dimensional schematic illustration of anatomicalstructures of the eye relevant to the surgical treatment enabled by theintegrated surgical system 1000. To reduce the TOP, laser treatmenttargets ocular tissues that affect the trabecular outflow pathway 40.These ocular tissues may include the trabecular meshwork 12, the scleralspur 14, the Schlemm's canal 18, and the collector channels 19. Thetrabecular meshwork 12 has three layers, the uveal 15, the corneoscleralmeshwork 16, and the juxtacanalicular tissue 17. These layers are porousand permeable to aqueous, with the uveal 15 being the most porous andpermeable, followed by the corneoscleral meshwork 16. The least porousand least permeable layer of the trabecular meshwork 12 is thejuxtacanalicular tissue 17. The inner wall 18 a of the Schlemm's canal18, which is also porous and permeable to aqueous, has characteristicssimilar to the juxtacanalicular tissue 17.

FIG. 12 includes a three-dimensional illustration of a treatment patternP1 to be applied by the integrated surgical system 1000 to affect thesurgical volume 900 of ocular tissue shown in FIG. 11, and atwo-dimensional schematic illustration of the treatment pattern P1overlaying anatomical structures to be treated. FIG. 13 is athree-dimensional schematic illustration of the anatomical structures ofthe eye including an opening 902 through the that results from theapplication of the laser treatment pattern of FIG. 12. The opening 902provides and outflow pathway 40 that reduces the flow resistance in theocular tissue to increase aqueous flow from the anterior chamber 7 intothe Schlemm's canal 18 and thereby reduce the IOP of the eye.

Surgical treatments reduce outflow pathway resistance while minimizingocular tissue modification through design and selection of lasertreatment patterns. A treatment pattern is considered to define acollection of a laser-tissue interaction volumes, referred to herein ascells. The size of a cell is determined by the extent of the influenceof the laser-tissue interaction. When the laser spots, or cells, arespaced close along a line, the laser creates a narrow, microscopicchannel. A wider channel can be created by closely spacing a multitudeof laser spots within the cross section of the channel. The arrangementof the cells may resemble the arrangement of atoms in a crystalstructure.

With reference to FIG. 12, a treatment pattern P1 may be in the form ofa cubic structure that encompasses individual cells arranged inregularly spaced rows, columns and sheets or layers. The treatmentpattern P1 may be characterized by x, y, z dimensions, with x, y, zcoordinates of the cells being calculated sequentially from neighbor toneighbor in the order of a column location (x coordinate), a rowlocation (y coordinate), and a layer location (z coordinate). Atreatment pattern P1 as such, defines a three-dimensional model ofocular tissue to be modified by a laser or a three-dimensional model ofocular fluid to be affected by a laser.

A treatment pattern P1 is typically defined by a set of surgicalparameters. The surgical parameters may include one or more of atreatment area A that represents a surface area or layer of oculartissue through which the laser will travel. The treatment area A isdetermined by the treatment height, h, and the lateral extent of thetreatment, w. A treatment thickness t that represents the level to whichthe laser will cut into the ocular tissue from the distal extent orborder of the treatment volume at or near Schlemm's canal 18 to theproximal extent or border at or near the surface of the trabecularmeshwork 12. Thus, a laser applied in accordance with a treatmentpattern may affect or produce a surgical volume that resembles thethree-dimensional model of the treatment pattern, or may affect fluidlocated in an interior of an eye structure resembled by thethree-dimensional model.

Additional surgical parameters define the placement of the surgicalvolume or affected volume within the eye. For example, with reference toFIGS. 11 and 12, placement parameters may include one or more of alocation l that represents where the treatment is to occur relative tothe circumferential angle of the eye, and a treatment depth d thatrepresents a position of the three-dimensional model of ocular tissue orocular fluid within the eye relative to a reference eye structure. Inthe following, the treatment depth d is shown and described relative tothe region where the anterior chamber 7 meets the trabecular meshwork12. Together, the treatment pattern and the placement parameters definea treatment plan.

A femtosecond laser provides highly localized, non-thermalphoto-disruptive laser-tissue interaction with minimal collateral damageto surrounding ocular tissue. Photo-disruptive interaction of the laseris utilized in optically transparent tissue. The principal mechanism oflaser energy deposition into the ocular tissue is not by absorption butby a highly nonlinear multiphoton process. This process is effectiveonly at the focus of the pulsed laser where the peak intensity is high.Regions where the beam is traversed but not at the focus are notaffected by the laser. Therefore, the interaction region with the oculartissue is highly localized both transversally and axially along thelaser beam.

With reference to FIGS. 11 and 12, in accordance with embodimentsdisclosed herein a surgical volume 900 of ocular tissue to be treated isidentified by the integrated surgical system 1000 and a treatmentpattern P1 corresponding to the surgical volume is designed by theintegrated surgical system. Alternatively, the treatment pattern P1 maybe designed first, and then an appropriate surgical volume 900 forapplying the treatment pattern may be identified. The surgical volume900 of ocular tissue may comprise portions of the trabecular meshwork 12and the Schlemm's canal 18. For example, the surgical volume 900 ofocular tissue shown in FIG. 11 includes portions of the uveal 15, thecorneoscleral meshwork 16, the juxtacanalicular tissue 17, and the innerwall 18 a of the Schlemm's canal 18. The treatment pattern P1 defines alaser scanning procedure whereby a laser is focused at different depthlocations in ocular tissue and then scanned in multiple directions toaffect a three-dimensional volume of tissue comprising multiple sheetsor layers of affected tissue.

With reference to FIGS. 12 and 13, during a laser scanning procedure, asurgical laser 701 may scan ocular tissue in accordance with thetreatment pattern P1 to form an opening 902 that extends from theanterior chamber 7, through each of the uveal 15, the corneoscleralmeshwork 16, the juxtacanalicular tissue 17 of the trabecular meshwork12, and the inner wall 18 a of the Schlemm's canal 18. While the exampleopening 902 in FIG. 13 is depicted as a continuous, single lumendefining a fluid pathway, the opening may be defined an arrangement ofadjacent pores forming a sponge like structure defining a fluid pathwayor a combination thereof. While the example opening 902 in FIG. 13 is inthe shape of a cube, the opening may have other geometric shapes.

The movement of the laser as it scans to affect the surgical volume 900follows the treatment pattern P1, which is defined by a set of surgicalparameters that include a treatment area A and a thickness t. Thetreatment area A is defined by a width w and a height h. The width maybe defined in terms of a measure around the circumferential angle. Forexample, the width w may be defined in terms of an angle, e.g., 90degrees, around the circumferential angle.

Referring to FIGS. 11 and 12, an initial placement of the laser focuswithin the eye is defined by a set of placement parameters, including adepth d and a location l. The location l defines a point around thecircumferential angle of the eye at which laser treatment will begin,while the depth d defines a point between the anterior chamber 7 and theSchlemm's canal 18 where the laser treatment begins or ends. The depth dis measured relative to the region where the anterior chamber 7 meetsthe trabecular meshwork 12. Thus, a first point that is closer to theSchlemm's canal 18 side of the trabecular meshwork 12 may be describedas being deeper than a second point that is closer to the anteriorchamber 7 side of the trabecular meshwork 12. Alternatively, the secondpoint may be described as being shallower than the first point.

With reference to FIG. 13, the opening 902 resulting from laserapplication of the treatment pattern P1 resembles the surgical volume900 and is characterized by an area A and thickness t similar to thoseof the surgical volume and the treatment pattern. The thickness t of theresulting opening 902 extends from the anterior chamber 7 and throughthe inner wall 18 a of the Schlemm's canal 18, while the area A definesthe cross-section size of the opening 902.

In accordance with embodiments disclosed herein, during a laser scanningprocedure, a laser focus is moved to different depths d in ocular tissueand then scanned in two lateral dimensions or directions as defined by atreatment pattern P1 to affect a three-dimensional volume 900 of oculartissue comprising multiple sheets or layers of affected tissue. The twolateral dimensions are generally orthogonal to the axis of movement ofthe laser focus. With reference to FIG. 13, the movement of a laserfocus during laser scanning is described herein with reference to x, y,and z directions or axes, wherein: 1) movement of the laser focus todifferent depths d through the thickness t of treatment pattern P1 orthe volume 900 of tissue corresponds to movement of the focus along thez axis, 2) movement of the laser focus in two dimensions or directionsorthogonal to the z axis corresponds to movement of the laser focusalong the width w of the treatment pattern P1 or the volume 900 oftissue in the x direction, and movement of the laser focus along theheight h of the treatment pattern P1 or the volume 900 of tissue in they direction.

As used herein scanning of the laser focus generally corresponds to araster type movement of the laser focus in the x direction, the ydirection, and the z direction. The laser focus may be located at apoint in the z direction and then raster scanned in two dimensions ordirections, in the x direction and the y direction. The focal point ofthe laser in the z direction may be referred to as a depth d within thetreatment pattern P1 or the volume 900 of tissue. The two directionraster scanning of the laser focus defines a layer of laser scanning,which in turn produces a layer of laser-affected tissue.

During laser scanning, pulse shots of a laser are delivered to tissuewithin the volume of ocular tissue corresponding to the treatmentpattern P1. Because the laser interaction volume is small, on the orderof a few micrometers (m), the interaction of ocular tissue with eachlaser shot of a repetitive laser breaks down ocular tissue locally atthe focus of the laser. Pulse duration of the laser for photo-disruptiveinteraction in ocular tissue can range from several femtoseconds toseveral nanoseconds and pulse energies from several nanojoules to tensof microjoules. The laser pulses at the focus, through multiphotonprocesses, breaks down chemical bonds in the molecules, locallyphoto-dissociate tissue material and create gas bubbles in wet tissue.The breakdown of tissue material and mechanical stress from bubbleformation fragments the tissue and create clean continuous cuts when thelaser pulses are laid down in proximity to one another along geometricallines and surfaces.

Table 2 includes examples of treatment pattern parameters and surgicallaser parameters for treating tissue. The range of the parameter set islimited by practical ranges for the repetition rate of the laser and thescanning speed of the scanners.

TABLE 2 Treatment pattern dimensions Opening Cell size Laser Laser Laserw[mm], Cross w[μm], average repetition pulse Procedure Tissue h[mm],section A h[μm], power rate energy time treated t[mm] [mm²] t[μm] [W][kHz] [μJ] [s] Trabecular 1.5, 0.2, 0.2 0.3 3, 3, 3 0.9 300 3 7.4meshwork Trabecular 2, 0.2, 0.2 0.4 4, 4, 4 1 200 5 6.3 meshwork

With reference to FIGS. 11, 12, 13, 14 a and 14 b, in one type of laserscanning procedure, the scanning begins at the end of the treatmentpattern P1 adjacent the anterior chamber 7 and proceeds in a directionthat generally corresponds to the direction of propagation of the laser701. More specifically, and with reference to FIG. 14a , the laserscanning proceeds in the z direction toward an anatomical structure,e.g., the inner wall 18 a of the Schlemm's canal 18, while the directionof propagation of the laser 701 also proceeds toward same anatomicalstructure, e.g., the inner wall 18 a of the Schlemm's canal 18.

Laser scanning in this manner, however, may be ineffective at producingthe desired opening 902 between the anterior chamber 7 and the Schlemm'scanal 18 due to interference by gas bubbles produced during laserapplication. As noted above, femtosecond lasers generate a very shortpulse of optical energy. When a beam of such pulses is focused to a verysmall volume of space characterized by a small cross-sectional area, anon-linear effect occurs within the focus spot. When such a focus spotis directed onto tissue, the tissue is photodisrupted (broken down)leaving a small bubble of gas. This process is essentially non-thermaland requires a tiny amount of energy. The result is that the surroundingtissue is not affected.

However, when a femtosecond laser beam is scanned over the surface of atissue, the laser treatment of this initial surface layer generates alayer of bubbles over the area of the treatment. When the laser scansthe layer of tissue below or deeper than the initial surface layer,these bubbles create a shadow effect that scatters the incident laserlight, effectively blocking further treatment of the tissue. Thisrenders further laser treatment of tissue beneath or deeper that theinitial surface layer ineffective.

An example of this effect within the context of glaucoma surgery isillustrated in FIGS. 14a and 14b . In FIG. 14a , the focus of the laserbeam 701 is initially located at a depth d₁. This depth d₁ places thelaser focus in an initial layer 904 of tissue. For example, initiallayer 904 of tissue may be at the interface between the uveal 15 of thetrabecular meshwork 12 and the anterior chamber 7. In this instance,this depth location of the laser focus is referred to a null depth andthe initial layer 904 to be treated corresponds to the surface of theuveal 15 facing the anterior chamber 7. Once the laser focus ispositioned at the initial depth d₁, the focus is scanned in multipledirections while being maintained at the initial depth. With referenceto FIG. 14a , the multiple directions are the x direction and ydirection, where the x direction is into the plane of FIG. 14 a.

With reference to FIG. 14b , the raster scanning in the multipledirections results in the photodisruption of the initial layer 904 oftissue and the formation of a layer of bubbles 906 at the initial layerof tissue. The focus of the laser beam 701 is then moved in the zdirection toward the inner wall 18 a of the Schlemm's canal 18 toanother depth d₂. This depth d₂ places the laser focus at a subsequentlayer 908 of tissue deeper than the initial layer 904. For example, thedeeper layer of tissue may comprise the uveal 15 of the trabecularmeshwork 12. Once the laser focus is positioned at the subsequent layer908, the focus is raster scanned in multiple directions while beingmaintained at that depth. However, in this instance, the layer ofbubbles 906 scatters the incident laser light, effectively blockingfurther treatment of the tissue at the subsequent layer 908.

With reference to FIGS. 11, 12, 13, 15 a-15 g, in accordance withembodiments disclosed the above ineffective laser treatment is avoidedby implementing a laser scanning procedure, whereby the laser scanningbegins at the end of the treatment pattern P1 adjacent the Schlemm'scanal 18 and proceeds in a direction generally opposite to or againstthe direction of propagation of the laser 701. More specifically, andwith reference to FIG. 15a , the laser scanning starts at an anatomicalstructure, e.g., the inner wall 18 a of the Schlemm's canal 18 andproceeds away from that structure in the z direction toward the anteriorchamber 7, while the direction of propagation of the laser 701 proceedstoward the that structure.

With this scanning procedure, the laser beam of femtosecond pulses isfocused within a volume of ocular tissue at an initial depth or distancefrom a surface of the volume of tissue. An initial layer of tissue atthe initial depth is treated, which generates a layer of bubbles at thearea of the initial layer. After treatment of the initial layer oftissue, the laser is refocused to a subsequent layer of tissue that isshallower than the initial layer of tissue, i.e., at a depth that iscloser to the surface of the volume of ocular tissue than the initialdepth. Since the layer of bubbles at the area of the initial layer isbelow the second layer, the bubbles do not obstruct the second layer.This process is repeated until the laser scans, layer-by-layer throughthe volume of ocular tissue to the surface of the volume of tissue.

An example of this scanning procedure within the context of glaucomasurgery is illustrated in FIGS. 15a-15g . In FIG. 15a , the focus of thelaser beam 701 is initially located at a depth d₁. This depth d₁ placesthe laser focus in an initial layer 910 of tissue. For example, initiallayer 910 of tissue may comprise the inner wall 18 a of the Schlemm'scanal 18. Once the laser focus is positioned at the initial depth d₁,the focus is scanned in multiple directions while being maintained atthe initial depth d₁. With reference to FIG. 15a , the multipledirections are the x direction and y direction, where the x direction isinto the plane of FIG. 15 a.

With reference to FIG. 15b , the laser scanning in multiple directionsresults in the photodisruption of the initial layer 910 of tissue andthe formation of a layer of bubbles 912 at the location of the initiallayer of tissue. The focus of the laser beam 701 is then moved in the zdirection toward the anterior chamber 7 to a subsequent depth d₂. Thesubsequent depth d₂ places the laser focus at a subsequent layer 914 oftissue less deep than the initial layer 910 of tissue. For example, thesubsequent layer 914 of tissue may comprise a portion of the inner wall18 a of the Schlemm's canal 18, the juxtacanalicular tissue 17, and thecorneoscleral meshwork 16. Once the laser focus is positioned at thesubsequent depth d₂, the focus is scanned in multiple directions whilebeing maintained at the subsequent depth d₂. Since the layer of bubbles912 is beneath the subsequent layer 914, the bubbles do not obstructlaser access to or block photodisruption of the subsequent layer.

With reference to FIG. 15c , the laser scanning in multiple directionsresults in the photodisruption of the subsequent layer 914 of tissue andthe formation of a layer of bubbles 916 at the location of thesubsequent layer of tissue. The focus of the laser beam 701 is thenmoved in the z direction toward the anterior chamber 7 to a subsequentdepth d₃. The subsequent depth d₃ places the laser focus at a subsequentlayer 918 of tissue less deep than the subsequent layer 914 of tissue.For example, the subsequent layer 914 of tissue may comprise a portionof the juxtacanalicular tissue 17 and the corneoscleral meshwork 16.Once the laser focus is positioned at the subsequent depth d₃, the focusis scanned in multiple directions while being maintained at thesubsequent depth d₃. Since the layers of bubbles 912, 916 are beneaththe subsequent layer 918, the bubbles do not obstruct laser access to orblock photodisruption of the subsequent layer.

With reference to FIG. 15d , the laser scanning in multiple directionsresults in the photodisruption of the subsequent layer 918 of tissue andthe formation of a layer of bubbles 920 at the location of thesubsequent layer of tissue. The focus of the laser beam 701 is thenmoved in the z direction toward the anterior chamber 7 to a subsequentdepth d₄. The subsequent depth d₄ places the laser focus at a subsequentlayer 922 of tissue less deep than the subsequent layer 918 of tissue.For example, the subsequent layer 922 of tissue may comprise a portionof the corneoscleral meshwork 16 and the uveal 15. Once the laser focusis positioned at the subsequent depth d₄, the focus is scanned inmultiple directions while being maintained at the subsequent depth d₄.Since the layers of bubbles 912, 916, 920 are beneath the subsequentlayer 922, the bubbles do not obstruct laser access to or blockphotodisruption of the subsequent layer.

With reference to FIG. 15e , the laser scanning in multiple directionsresults in the photodisruption of the subsequent layer 922 of tissue andthe formation of a layer of bubbles 924 at the location of thesubsequent layer of tissue. The focus of the laser beam 701 is thenmoved in the z direction toward the anterior chamber 7 to a subsequentdepth d₅. The subsequent depth d₅ places the laser focus at a subsequentlayer 926 of tissue less deep than the subsequent layer 922 of tissue.For example, the subsequent layer 926 of tissue may comprise the uveal15. Once the laser focus is positioned at the subsequent depth d₅, thefocus is scanned in multiple directions while being maintained at thesubsequent depth d₅. Since the layers of bubbles 912, 916, 920, 924 arebeneath the subsequent layer 926, the bubbles do not obstruct laseraccess to or block photodisruption of the subsequent layer.

With reference to FIG. 15f , the laser scanning in multiple directionsresults in the photodisruption of the subsequent layer 926 of tissue andthe formation of a layer of bubbles 928 at the location of thesubsequent layer of tissue. The focus of the laser beam 701 is thenmoved in the z direction toward the anterior chamber 7 to a subsequentdepth d₆. The subsequent depth d₆ places the laser focus at a subsequentlayer 930 of tissue less deep than the subsequent layer 926 of tissue.For example, the subsequent layer 930 of tissue may comprise the uveal15 and the inner surface of the uveal facing the anterior chamber 7.Once the laser focus is positioned at the subsequent depth d₆, the focusis scanned in multiple directions while being maintained at thesubsequent depth d₆. Since the layers of bubbles 912, 916, 920, 924, 928are beneath the subsequent layer 930, the bubbles do not obstruct laseraccess to or block photodisruption of the subsequent layer.

With reference to FIG. 15g , the laser scanning in multiple directionsresults in the photodisruption of the subsequent layer 930 of tissue andthe formation of a layer of bubbles 932 at the location of thesubsequent layer of tissue. Photodisruption of this subsequent layer 930of tissue results in the formation of an opening 902 between theanterior chamber 7 and the Schlemm's canal 18, thus completing the lasertreatment procedure.

With reference to FIG. 16a , upon completion of the laser scanning theopening 902 may be partially obstructed or occluded by the gas bubbles912, 916, 920, 924, 928 created during treatment. Thus, in accordancewith embodiments disclosed herein, the direction of the laser scanningdescribed with reference to FIGS. 15a-15g may be reversed in order topush any remaining bubbles into the Schlemm's canal 18 thereby clearingthe opening 902, as shown in FIG. 16 b.

FIG. 17 is a flowchart of a method of treating a target volume of oculartissue with a laser having a direction of propagation toward the targetvolume of ocular tissue. With reference to FIG. 12, the target volume 60of ocular tissue is characterized by a distal extent 62, a proximalextent 64, and a lateral extent 66. The distal extent 62 corresponds tothe part or point of the target volume 60 that is most distal along thedirection of propagation of the laser 701. The proximal extent 64corresponds to the part or point of the target volume 60 that is mostproximal along the direction of propagation of the laser 701. Thelateral extent 66 corresponds to the distance or width w of the targetvolume 60 along the circumference angle.

The method, which may be performed by the integrated surgical system1000 of FIGS. 7-10 b, begins at a point in a surgical procedure whereaccess to the irido-corneal angle has already been obtained and thetarget volume 60 of ocular tissue has already been identified fortreatment. Systems and methods for accessing the irido-corneal angle aredescribed in U.S. patent application Ser. No. 16/036,883, entitledIntegrated Surgical System and Method for Treatment in the Irido-CornealAngle of the Eye, the disclosure of which is hereby incorporated byreference. Systems and method for identifying volumes of ocular tissuefor treatment and designing treatment patterns reference are describedin U.S. patent application Ser. No. 16/125,588, entitled Non-Invasiveand Minimally Invasive Laser Surgery for the Reduction of IntraocularPressure in the Eye, the disclosure of which is hereby incorporated byreference.

At block 1702, the integrated surgical system 1000 initiallyphotodisrupts tissue at an initial depth d₁ corresponding to the distalextent 62 of the target volume 60 of ocular tissue is. To this end, andwith reference to FIG. 15a , the integrated surgical system 1000 focuseslight from a femtosecond laser 701 at a spot in the tissue at theinitial depth d₁ and applies optical energy to the tissue, which energyis at a level sufficient to photodisrupt the tissue. Optical energy isapplied by scanning the laser 701 in multiple directions defining aninitial treatment plane 910 at the initial depth d₁ to therebyphotodisrupt an initial layer of tissue of the target volume of oculartissue. With reference to FIG. 13, the scanning may be in the form of araster scan where the laser is scanned in a first direction along thelateral extent 66, i.e., the x direction, and then slightly repositionedin a second direction. i.e., the y direction, and then scanned againalong the lateral extent.

As an additional aspect of the initial photodisruption process of block1702, the integrated surgical system 1000 may detect the distal extent62 of the target volume of ocular tissue. To this end, in oneconfiguration images captured by the OCT imaging apparatus 300 areprocessed by the control system 100 to detect the distal extent 62 ofthe target volume using known techniques. In another configuration, theintegrated surgical system 1000 may include a multiphoton imagingapparatus (not shown) that provides a visual indication on a display ofthe user interface 110 that is indicative of the location of the focusof the laser 701 relative to the distal extent 62 of the target volume60 of ocular tissue. The integrated surgical system 1000 may alsodetermine the lateral extent 66 of the target volume 60 of ocular tissuebased on OCT imaging.

At block 1704 and with reference to FIGS. 15b-15f , the integratedsurgical system 1000 subsequently photodisrupts tissue at one or moresubsequent depths d₂-d₆ between the distal extent 62 of the targetvolume 60 of ocular tissue and the proximal extent 64 of the targetvolume of ocular tissue is by moving a focus of the laser 701 in adirection opposite the direction of propagation of the laser. To thisend, the integrated surgical system 1000 focuses light from afemtosecond laser 701 at a spot in the tissue at the one or moresubsequent depths d₂-d₆ and applies optical energy to the tissue, whichenergy is at a level sufficient to photodisrupt the tissue. Opticalenergy is applied by scanning the laser 701 in multiple directionsdefining a subsequent treatment plane 914, 918, 922, 926, 930 at arespective different depth d₂-d₆, to thereby photodisrupt one or moresubsequent layers of tissue of the target volume 60 of ocular tissue.With reference to FIG. 13, the scanning may be in the form of a rasterscan where the laser is scanned in a first direction along the lateralextent 66, i.e., the x direction, and then slightly repositioned in asecond direction. i.e., the y direction, and then scanned again alongthe lateral extent.

As an additional aspect of the subsequent photodisruption process ofblock 1704, the integrated surgical system 1000 may detect the proximalextent 64 of the target volume 60 of ocular tissue. To this end, in oneconfiguration images captured by the OCT imaging apparatus 300 areprocessed by the control system 100 to detect the proximal extent 64 ofthe target volume 60 using known techniques. In another configuration,the integrated surgical system 1000 may include a multiphoton imagingapparatus (not shown) that provides a visual indication on a display ofthe user interface 110 that is indicative of the location of the focusof the laser 701 relative to the proximal extent 64 of the target volume60 of ocular tissue. In yet another configuration, the integratedsurgical system 1000 may include an opto-mechanical imaging apparatus(not shown) that provides a visual indication on a display of the userinterface 110 that is indicative of the location of the focus of thelaser 701 relative to the proximal extent 64 of the target volume 60 ofocular tissue.

At block 1706, the integrated surgical system 1000 determines if theproximal extent 64 of the target volume 60 of ocular tissue has beenphotodisrupted. If the proximal extent 64 has not been photodisrupted,the process return to block 1704 and the integrated surgical system 1000repeats the photodisrupting at one or more subsequent depths untiltissue at the proximal extent 64 of the target volume 60 of oculartissue is photodisrupted.

Returning to block 1706 and with reference to FIG. 16a , if the proximalextent 64 has been photodisrupted, the process proceeds to block 1708and the integrated surgical system 1000 photodisrupts tissue debris orbubbles 906 between the proximal extent 64 of the target volume 60 ofocular tissue and the distal extent 62 of the target volume by movingthe focus of the laser 701 in the direction of propagation of the laser.To this end, the integrated surgical system 1000 focuses light from afemtosecond laser 701 at a spot in the volume of tissue debris orbubbles 906 at the one or more subsequent depths and applies opticalenergy to the tissue debris or bubbles. Optical energy is applied byscanning the laser 701 in multiple directions along one or more of thepreviously-scanned treatment planes 910, 914, 918, 922, 926, 930 tophotodisrupt tissue debris or bubbles 906 between the proximal extent 64and the distal extent 62 of the photodisrupted target volume 60.

At block 1710, the integrated surgical system 1000 may determine torepeat the treatment of the photodisrupted target volume 60 of oculartissue or to end the treatment. If treatment is repeated, the processreturns to block 1702, where the integrated surgical system 1000 repeatsthe initial photodisrupting of tissue, and then proceeds to blocks 1704and 1706, where the system repeats the subsequent photodisrupting oftissue one or more times. If treatment is not to be repeated, theprocess proceeds to block 1712, where treatment ends.

Regarding the use of a multiphoton imaging apparatus to detect thedistal extent 62 of the target volume of ocular tissue, or the proximalextent 64 of the target volume, such an apparatus is configured topresent an image of a second harmonic light that results from anencounter between the focus of the laser 701 and tissue. When the focusof the laser 701 is not encountering tissue, the intensity of the secondharmonic light is zero or very low. When the focus is encounteringtissue, the intensity of the second harmonic light increases. Based onthis, a distal extent 62 such as shown in FIG. 12 may be detected byfirst advancing the focus of the laser 701 through the trabecularmeshwork 12 and the inner wall 18 a of the Schlemm's canal and into theSchlemm's canal 18, where the focus will not encounter light and theintensity of the second harmonic light is zero or very low, and thenretracting the focus back toward the inner wall 18 a of the Schlemm'scanal and detecting that the focus is at the inner wall when an increasein the intensity of the second harmonic light is noted on the display.

Regarding the use of an opto-mechanical imaging apparatus to detect theproximal extent 64 of the target volume 60 of ocular tissue, such anapparatus is configured to direct a first beam of light and a secondbeam of light to be incident with the target volume and to align thefirst beam of light and the second beam of light relative to each otherand relative to the laser beam such that the first beam of light and thesecond beam light intersect at a point corresponding to the focus of thelaser. The apparatus is also configured to capture an image of a firstspot corresponding to the first beam of light, and a second spotcorresponding to the second beam of light relative to the proximalextent 64 of the target volume 60 of ocular tissue. The first and secondspots appear in the image as two separate visible spots on the surfaceof the proximal extent 64 when the focus is away from the surface, andas a single, overlapping spot when the focus is on the surface.Accordingly, the proximal extent 64 is detected when the spots overlap.

With reference to FIGS. 7-10 b, a surgical system 1000 for implementingthe method of FIG. 17 includes a first optical subsystem 1001 includinga focusing objective 700 configured to be coupled to the eye 1, and asecond optical subsystem 1002 including a laser source 200 configured tooutput a laser beam 201/701. The second optical subsystem 1002 alsoincludes a plurality of components 1003 configured to one or more offocus, scan, and direct the laser beam through the focusing objective,in a direction of propagation toward the target volume of ocular tissue.

The surgical system 1000 further includes a control system 100 coupledto the second optical subsystem 1002 and configured to control the focusand scan of the laser beam 701 to photodisrupt tissue at an initialdepth corresponding to the distal extent of the target volume of oculartissue. To this end, the control system 100 is configured to focus lightfrom a femtosecond laser source 200 at a spot in the tissue at theinitial depth and then apply optical energy to the tissue, where theenergy is sufficient to photodisrupt tissue. The control system 100controls the focus and scan of the laser beam 701 during application ofoptical energy by being further configured to scan the laser in multipledirections defining an initial treatment plane, to thereby photodisruptan initial layer of tissue of the target volume of ocular tissue.

The control system 100 is also configured to control the focus and scanof the laser beam 701 to photodisrupt tissue at one or more subsequentdepths between the distal extent of the target volume of ocular tissueand the proximal extent of the target volume of ocular tissue by movinga focus of the laser in a direction opposite the direction ofpropagation of the laser. To this end, the control system 100 isconfigured to focus light from a femtosecond laser source 200 at a spotin the tissue at a subsequent depth and then apply optical energy to thetissue, where the energy is sufficient to photodisrupt tissue. Thecontrol system 100 controls the focus and scan of the laser beam 701during application of optical energy by being further configured to scanthe laser in multiple directions defining a subsequent treatment plane,to thereby photodisrupt a subsequent layer of tissue of the targetvolume of ocular tissue.

The control system 100 is also configured to control the focus and scanof the laser beam 701 to photodisrupt tissue debris or bubbles betweenthe proximal extent of the target volume of ocular tissue and the distalextent of the target volume by moving the focus of the laser in thedirection of propagation of the laser, after photodisrupting the targetvolume of ocular tissue. The control system 100 is further configured tocontrol the focus and scan of the laser beam 701 to repeat the initialphotodisrupting of tissue and the subsequent photodisrupting of tissueone or more times.

FIG. 18 is a flowchart of a method of treating an eye comprising ananterior chamber, a Schlemm's canal, and a trabecular meshworktherebetween. The method, which may be performed by the integratedsurgical system 1000 of FIGS. 7-10 b, begins at a point in a surgicalprocedure where access to the irido-corneal angle has already beenobtained and one or more anatomical structures of the eye that are to betreated have been located.

At block 1802 and with reference to FIGS. 15a and 15b , the integratedsurgical system 1000 initially photodisrupts ocular tissue at or near aninterface of an inner wall 18 a of the Schlemm's canal 18 and thetrabecular meshwork 12. To this end, the integrated surgical system 1000focuses light from a femtosecond laser 701 at a spot in the oculartissue at or near the interface of the inner wall 18 a of the Schlemm'scanal 18 and the trabecular meshwork 12 and applies optical energy tothe tissue, which energy is at a level sufficient to photodisrupt thetissue.

As an additional aspect of the initial photodisruption process of block1802, the integrated surgical system 1000 may detect ocular tissue at ornear the interface of the inner wall 18 a of the Schlemm's canal 18 andthe trabecular meshwork 12. To this end, in one configuration imagescaptured by the OCT imaging apparatus 300 are processed by the controlsystem 100 to detect the interface of the inner wall 18 a of theSchlemm's canal 18 and the trabecular meshwork 12 using knowntechniques. In another configuration, the integrated surgical system1000 may include a multiphoton imaging apparatus (not shown) thatprovides a visual indication on a display of the user interface 110 thatis indicative of the location of the focus of the laser 701 relative tothe interface of the inner wall 18 a of the Schlemm's canal 18 and thetrabecular meshwork 12. The integrated surgical system 1000 may alsodetermine a lateral extent 66 of ocular tissue to be photodisruptedbased on OCT imaging.

At block 1804 and with reference to FIGS. 15c-15f , the integratedsurgical system 1000 subsequently photodisrupts ocular tissue of thetrabecular meshwork 12. To this end, the integrated surgical system 1000focuses light from a femtosecond laser 701 at a spot in tissue of thetrabecular meshwork 12 and applies optical energy to the tissue, whichenergy is at a level sufficient to photodisrupt the tissue.

As an additional aspect of the subsequent photodisruption process ofblock 1804, the integrated surgical system 1000 may detect a proximalextent of tissue of the trabecular meshwork. To this end, in oneconfiguration images captured by the OCT imaging apparatus 300 areprocessed by the control system 100 to detect the proximal extent 64 ofthe tissue of the trabecular meshwork using known techniques. In anotherconfiguration, the integrated surgical system 1000 may include amultiphoton imaging apparatus (not shown) that provides a visualindication on a display of the user interface 110 that is indicative ofthe location of the focus of the laser 701 relative to the proximalextent 64 of the tissue of the trabecular meshwork. In yet anotherconfiguration, the integrated surgical system 1000 may include anopto-mechanical imaging apparatus (not shown) that provides a visualindication on a display of the user interface 110 that is indicative ofthe location of the focus of the laser 701 relative to the proximalextent 64 of the tissue of the trabecular meshwork

At block 1806, the integrated surgical system 1000 determines if anopening is formed between the anterior chamber and the Schlemm's canal.If an opening has not been formed, the process return to block 1802 andthe integrated surgical system 1000 repeats the initial photodisruptingof ocular tissue and then proceeds to block 1804 and repeats thesubsequent photodisrupting of ocular tissue one or more times until anopening is formed between the anterior chamber and the Schlemm's canal.If an opening has been formed, the process proceeds to block 1808, wheretreatment ends.

With reference to FIGS. 7-10 b, a system 1000 for implementing themethod of FIG. 18 includes a first optical subsystem 1001 including afocusing objective 700 configured to be coupled to the eye 1, and asecond optical subsystem 1002 including a laser source 200 configured tooutput a laser beam 201/701. The second optical subsystem 1002 alsoincludes a plurality of components 1003 configured to one or more offocus, scan, and direct the laser beam through the focusing objective,toward ocular tissue.

The surgical system 1000 further includes a control system 100 coupledto the second optical subsystem 1002 and configured to control the focusand scan of the laser beam 701 to initially photodisrupt ocular tissueat or near an interface of an inner wall of the Schlemm's canal and thetrabecular meshwork. To this end, the control system 100 is configuredto focus light from a femtosecond laser source 200 at a spot in theocular tissue at or near the interface of the inner wall of theSchlemm's canal and the trabecular meshwork, and then apply optical tothe tissue, where the energy is sufficient to photodisrupt tissue.

The control system 100 is also configured to control the focus and scanof the laser beam 701 to subsequently photodisrupt tissue of thetrabecular meshwork. To this end, the control system 100 is configuredto focus light from a femtosecond laser at a spot in tissue of thetrabecular meshwork, and then apply optical energy to the tissue, wherethe energy is sufficient to photodisrupt tissue. The control system 100is further configured to control the focus and scan of the laser beam701 to repeat the initial photodisrupting of ocular tissue and thesubsequent photodisrupting of ocular tissue one or more times until anopening is formed between the anterior chamber and the Schlemm's canal.

The various aspects of this disclosure are provided to enable one ofordinary skill in the art to practice the present invention. Variousmodifications to exemplary embodiments presented throughout thisdisclosure will be readily apparent to those skilled in the art. Thus,the claims are not intended to be limited to the various aspects of thisdisclosure but are to be accorded the full scope consistent with thelanguage of the claims. All structural and functional equivalents to thevarious components of the exemplary embodiments described throughoutthis disclosure that are known or later come to be known to those ofordinary skill in the art are expressly incorporated herein by referenceand are intended to be encompassed by the claims. Moreover, nothingdisclosed herein is intended to be dedicated to the public regardless ofwhether such disclosure is explicitly recited in the claims. No claimelement is to be construed under the provisions of 35 U.S.C. § 112,sixth paragraph, unless the element is expressly recited using thephrase “means for” or, in the case of a method claim, the element isrecited using the phrase “step for.”

It is to be understood that the embodiments of the invention hereindescribed are merely illustrative of the application of the principlesof the invention. Reference herein to details of the illustratedembodiments is not intended to limit the scope of the claims, whichthemselves recite those features regarded as essential to the invention.

What is claimed is:
 1. A method of treating a target volume of oculartissue of an irido-corneal angle of an eye with a laser having adirection of propagation toward the target volume of ocular tissue, thetarget volume of ocular tissue characterized by a distal extent, aproximal extent, and a lateral extent, the method comprising: initiallyphotodisrupting tissue at an initial depth corresponding to the distalextent of the target volume of ocular tissue; and subsequentlyphotodisrupting tissue at one or more subsequent depths between thedistal extent of the target volume of ocular tissue and the proximalextent of the target volume of ocular tissue by moving a focus of thelaser in a direction opposite the direction of propagation of the laser.2. The method of claim 1, wherein the photodisrupting at one or moresubsequent depths is repeated at a plurality of different subsequentdepths until tissue at the proximal extent of the target volume ofocular tissue is photodisrupted.
 3. The method of claim 1, furthercomprising, after photodisrupting the target volume of ocular tissue,photodisrupting tissue debris or bubbles between the proximal extent ofthe target volume of ocular tissue and the distal extent of the targetvolume of ocular tissue by moving the focus of the laser in thedirection of propagation of the laser.
 4. The method of claim 1, whereininitially or subsequently photodisrupting tissue comprises: focusinglight from a femtosecond laser at a spot in the tissue at the initialdepth or at the one or more subsequent depths; and applying opticalenergy to the tissue.
 5. The method of claim 4, wherein applying opticalenergy comprises: scanning the laser in multiple directions defining atreatment plane, to thereby photodisrupt an initial layer of tissue ofthe target volume of ocular tissue or one or more subsequent layers oftissue of the target volume of ocular tissue.
 6. The method of claim 1,further comprising repeating the initial photodisrupting of tissue andthe subsequent photodisrupting of tissue one or more times.
 7. Themethod of claim 1, further comprising: detecting the distal extent ofthe target volume of ocular tissue; detecting the proximal extent of thetarget volume of ocular tissue; and determining the lateral extent ofthe target volume of ocular tissue.
 8. The method of claim 7, whereinthe distal extent of the target volume of ocular tissue and the proximalextent of the target volume of ocular tissue are detected based on oneor more images of ocular tissue.
 9. The method of claim 8, wherein theone or more images of ocular tissue are obtained using one or more ofoptical imaging techniques, multiphoton imaging techniques, andopto-mechanical imaging techniques.
 10. A method of treating an eyecomprising an anterior chamber, a Schlemm's canal, and a trabecularmeshwork therebetween, the method comprising: initially photodisruptingocular tissue at or near an interface of an inner wall of the Schlemm'scanal and the trabecular meshwork; and subsequently photodisruptingocular tissue of the trabecular meshwork.
 11. The method of claim 10,wherein initially photodisrupting ocular tissue comprises: focusinglight from a femtosecond laser at a spot in the ocular tissue at or nearthe interface of the inner wall of the Schlemm's canal and thetrabecular meshwork; and applying optical energy to the tissue.
 12. Themethod of claim 10, wherein subsequently photodisrupting tissuecomprises: focusing light from a femtosecond laser at a spot in tissueof the trabecular meshwork; and applying optical energy to the tissue.13. The method of claim 10, further comprising repeating the initialphotodisrupting of ocular tissue and the subsequent photodisrupting ofocular tissue one or more times until an opening is formed between theanterior chamber and the Schlemm's canal.
 14. The method of claim 10,further comprising: detecting ocular tissue at or near the interface ofthe inner wall of the Schlemm's canal and the trabecular meshwork;detecting a proximal extent of tissue of the trabecular meshwork; anddetermining a lateral extent of ocular tissue to be photodisrupted. 15.The method of claim 14, wherein ocular tissue at or near the interfaceof the inner wall of the Schlemm's canal and the trabecular meshwork,and tissue of the trabecular meshwork of are detected based on one ormore images of ocular tissue.
 16. The method of claim 15, wherein theone or more images of ocular tissue are obtained using one or more ofoptical imaging techniques, multiphoton imaging techniques, andopto-mechanical imaging techniques.